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[ { "id": "858bc74a-9832-4335-a2c6-9c5b69a9444c", "type": "title", "text": [ "Regional analysis on the occurrence of oral clefts in South America." ], "offsets": [ [ 0, 68 ] ] }, { "id": "00f3a882-295a-41e0-9f35-199d51f3614d", "type": "abstract", "text": [ "The aim of this work was to search for unequal birth prevalence rates (BPRs) of cleft lip +/- cleft palate (CL/P), and cleft palate only (CPO), among different geographic areas in South America, and to analyze phenotypic characteristics and associated risk factors in each identified cluster. Included were 5,128 CL/P cases, 1,745 CPO cases, and 3,712 controls (like-sexed, non-malformed liveborn infant, born immediately after a malformed one, in the same hospital), over 4,199,630 consecutive births. They were ascertained between 1967 and 2004, in 190 maternity hospitals of the ECLAMC (Estudio Colaborativo Latinoamericano de Malformaciones Congenitas) network, in 102 cities of all 10 South American countries. Non-predefined geographical areas with significantly unusual cleft BPRs were identified with Kulldorf and Nagarwalla's spatial scan statistic, employing number of cases and births, and exact location of each hospital. Expected values were cleft BPRs registered for the entire ECLAMC hospital network. Syndromic and non-syndromic clefts were considered for cluster analysis, and phenotypic characterization, while only non-syndromic for risk factor analysis. Seven clusters for CL/P, and four for CPO, with unusual BPRs were identified. CL/P cases in high BPR areas were more severe than elsewhere in the sample, similar to a previous ECLAMC report on microtia. For CL/P, high BPR clusters were associated with high altitude above sea level, Amerindian ancestry, and low socioeconomic strata; low BPR clusters showed association with African Black ancestry. Advanced maternal age, a recognized risk factor for CPO, was also associated with the only identified geographic cluster for CPO." ], "offsets": [ [ 69, 1776 ] ] } ]

[ { "id": "ef2ee7a8-ac46-413b-bc17-77b1bcd94126", "type": "Gene", "text": [ "sea" ], "offsets": [ [ 1520, 1523 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "adb3c7a1-5c3b-4cfa-83c5-f897375a9a8b", "type": "title", "text": [ "Evidence that common variation in NEDD9 is associated with susceptibility to late-onset Alzheimer's and Parkinson's disease." ], "offsets": [ [ 0, 134 ] ] }, { "id": "0d165432-7520-4c0d-ac3b-ff85a3d76f74", "type": "abstract", "text": [ "Late-onset Alzheimer's disease (LOAD) and Parkinson's disease (PD) are the most common neurodegenerative disorders and in both diseases susceptibility is known to be influenced by genes. We set out to identify novel susceptibility genes for LOAD by performing a large scale, multi-tiered association study testing 4692 single nucleotide polymorphism (SNPs). We identified a SNP within a putative transcription factor binding site in the NEDD9 gene (neural precursor cell expressed, developmentally down-regulated), that shows good evidence of association with disease risk in four out of five LOAD samples [N = 3521, P = 5.38x10(-6), odds ratio (OR) = 1.38 (1.20-1.59)] and in addition, we observed a similar pattern of association in two PD sample sets [N = 1464, P = 0.0145, OR =1.31 (1.05-1.62)]. In exploring a potential mechanism for the association, we observed that expression of NEDD9 and APOE show a strong inverse correlation in the hippocampus of Alzheimer's cases. These data implicate NEDD9 as a novel susceptibility gene for LOAD and possibly PD." ], "offsets": [ [ 135, 1210 ] ] } ]

[ { "id": "11a4dd00-060e-49d8-8c20-547c944229c0", "type": "Gene", "text": [ "NEDD9" ], "offsets": [ [ 34, 39 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f93c1612-e3b7-4683-9571-9e759c4d25a7", "type": "Gene", "text": [ "NEDD9" ], "offsets": [ [ 582, 587 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3724c765-ca40-4171-934e-60baeeb373cd", "type": "Gene", "text": [ "NEDD9" ], "offsets": [ [ 1032, 1037 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "468276e2-4c28-4fba-a252-1e64caace93d", "type": "Gene", "text": [ "APOE" ], "offsets": [ [ 1042, 1046 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d11aa228-70a5-4d5c-893e-96db321ebe28", "type": "Gene", "text": [ "NEDD9" ], "offsets": [ [ 1148, 1153 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "602fec7f-0fb9-46de-abdf-b6debfaa1342", "type": "title", "text": [ "Association between caffeine intake and risk of Parkinson's disease among fast and slow metabolizers." ], "offsets": [ [ 0, 106 ] ] }, { "id": "88216844-2555-445e-954f-0206c9b98f51", "type": "abstract", "text": [ "INTRODUCTION: Cytochrome P450 1A2 (CYP 1A2) is responsible for more than 90% of caffeine clearance. A polymorphic variant of CYP1A2 (-163C>A) (rs762551) is associated with high CYP1A2 inducibility. Both caffeine and its main metabolite, paraxanthine, may be neuroprotective. The association between caffeine intake and risk of Parkinson's disease (PD) in fast and slow caffeine metabolizers has not been compared. OBJECTIVE: In a case-control study, we analyzed the relationship between caffeine intake and risk of PD in both fast and slow caffeine metabolizers. METHODS: All the study participants were recruited prospectively, and interviewed for information on the amount and duration of caffeine intake. Genotyping of the CYP1A2 variant was carried out using the allelic discrimination method. RESULTS: Out of 1000 participants who were initially screened, 886 consisting of 418 PD and 468 race, sex and age matched controls were included. No evidence existed to suggest any association between CYP1A2 and the onset of PD (P=0.08). A significant association was seen between caffeine intake and the onset of PD (P=2.01x10(-5)), with the odds ratio for moderate and high drinkers at 0.71 [95% confidence interval (CI): 0.50-1.00] and 0.47 (95% CI: 0.34-0.65), respectively against the low drinkers. Multivariate analysis revealed no evidence of any interaction effects of caffeine with CYP1A2 (P=0.956). CONCLUSION: The association between caffeine intake and risk of PD was similarly observed in both fast and slow caffeine metabolizers, supporting experimental evidence in animal models that both caffeine and its major metabolite, paraxanthine, are neuroprotective." ], "offsets": [ [ 107, 1786 ] ] } ]

[ { "id": "3d240d15-59f1-479d-aec2-675392b1d830", "type": "Gene", "text": [ "Cytochrome P450 1A2" ], "offsets": [ [ 121, 140 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d7376b55-f4e5-44d0-86b1-48b80e315be7", "type": "Gene", "text": [ "CYP 1A2" ], "offsets": [ [ 142, 149 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "929a926b-9218-4f99-a8a0-2110874cc85b", "type": "Gene", "text": [ "CYP1A2" ], "offsets": [ [ 232, 238 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "25abe188-5c90-42ef-875c-bfaddbee4e26", "type": "Gene", "text": [ "CYP1A2" ], "offsets": [ [ 287, 293 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e15de776-6d68-4525-b726-1746548ffad4", "type": "Gene", "text": [ "CYP1A2" ], "offsets": [ [ 841, 847 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6a5e001e-b5da-4ad3-94ee-e2274de03684", "type": "Gene", "text": [ "CYP1A2" ], "offsets": [ [ 1114, 1120 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "46372e64-773f-429c-98fc-5ec767c84340", "type": "Gene", "text": [ "CYP1A2" ], "offsets": [ [ 1504, 1510 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "ee3dbd37-ea92-4680-9d26-f1ee3550019c", "type": "title", "text": [ "Mutation analysis of CHRNA1, CHRNB1, CHRND, and RAPSN genes in multiple pterygium syndrome/fetal akinesia patients." ], "offsets": [ [ 0, 115 ] ] }, { "id": "66798615-f1de-4b8a-a25e-f0ab1aca7ec1", "type": "abstract", "text": [ "Multiple pterygium syndromes (MPS) comprise a group of multiple congenital anomaly disorders characterized by webbing (pterygia) of the neck, elbows, and/or knees and joint contractures (arthrogryposis). MPS are phenotypically and genetically heterogeneous but are traditionally divided into prenatally lethal and nonlethal (Escobar) types. Previously, we and others reported that recessive mutations in the embryonal acetylcholine receptor g subunit (CHRNG) can cause both lethal and nonlethal MPS, thus demonstrating that pterygia resulted from fetal akinesia. We hypothesized that mutations in acetylcholine receptor-related genes might also result in a MPS/fetal akinesia phenotype and so we analyzed 15 cases of lethal MPS/fetal akinesia without CHRNG mutations for mutations in the CHRNA1, CHRNB1, CHRND, and rapsyn (RAPSN) genes. No CHRNA1, CHRNB1, or CHRND mutations were detected, but a homozygous RAPSN frameshift mutation, c.1177-1178delAA, was identified in a family with three children affected with lethal fetal akinesia sequence. Previously, RAPSN mutations have been reported in congenital myasthenia. Functional studies were consistent with the hypothesis that whereas incomplete loss of rapsyn function may cause congenital myasthenia, more severe loss of function can result in a lethal fetal akinesia phenotype." ], "offsets": [ [ 116, 1447 ] ] } ]

[ { "id": "7f532269-727a-43bf-b764-f53cba0acff9", "type": "Gene", "text": [ "CHRNA1" ], "offsets": [ [ 21, 27 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "70ee3f9d-8f09-4648-8a44-ab898734e906", "type": "Gene", "text": [ "CHRNB1" ], "offsets": [ [ 29, 35 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ee606489-809c-49eb-ad15-fee0be27245e", "type": "Gene", "text": [ "CHRND" ], "offsets": [ [ 37, 42 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2bc25f26-ce7e-45e3-9b6b-12e9f7b8d813", "type": "Gene", "text": [ "RAPSN" ], "offsets": [ [ 48, 53 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "049c539c-f96a-48ec-ae21-e51634083f0f", "type": "Gene", "text": [ "embryonal acetylcholine receptor g subunit" ], "offsets": [ [ 524, 566 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9ce98c7b-9cb7-4253-a653-8719b45acbf2", "type": "Gene", "text": [ "CHRNG" ], "offsets": [ [ 568, 573 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e1f10f52-15aa-4091-b9ca-150dbb35920b", "type": "FamilyName", "text": [ "acetylcholine receptor-related genes" ], "offsets": [ [ 713, 749 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d595faf4-209b-42ce-8320-4b4b448dd1e8", "type": "Gene", "text": [ "CHRNG" ], "offsets": [ [ 867, 872 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ff253221-c59e-4073-8ca8-a528621ed007", "type": "Gene", "text": [ "CHRNA1" ], "offsets": [ [ 904, 910 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1d1764b0-58d9-4b53-ad75-9a96ef06574a", "type": "Gene", "text": [ "CHRNB1" ], "offsets": [ [ 912, 918 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8aaa0d8b-66e1-4584-9a70-9c2048fc5bb4", "type": "Gene", "text": [ "CHRND" ], "offsets": [ [ 920, 925 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fb413e85-8f25-48ce-973e-8beef7ccef38", "type": "Gene", "text": [ "rapsyn" ], "offsets": [ [ 931, 937 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a82899a0-3bc8-46ed-95d8-07f1d432110c", "type": "Gene", "text": [ "RAPSN" ], "offsets": [ [ 939, 944 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "38c119bf-b10f-4a59-ba2d-3a718fe6cad1", "type": "Gene", "text": [ "CHRNA1" ], "offsets": [ [ 956, 962 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a18f117f-fd9a-45da-902a-1ced98b3c958", "type": "Gene", "text": [ "CHRNB1" ], "offsets": [ [ 964, 970 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d0dab293-8b9d-4084-a259-cd45cedb8cb8", "type": "Gene", "text": [ "CHRND" ], "offsets": [ [ 975, 980 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "42d4ec23-7d6b-43f2-a6c8-9203fb1d1122", "type": "Gene", "text": [ "RAPSN" ], "offsets": [ [ 1023, 1028 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "bc967738-a801-425e-9ded-8fee88d44a91", "type": "Gene", "text": [ "RAPSN" ], "offsets": [ [ 1173, 1178 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "22445abb-2515-4e6e-9b1f-de9ccc88a435", "type": "Gene", "text": [ "rapsyn" ], "offsets": [ [ 1321, 1327 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "fe320760-2e36-4a45-b33c-6f60cc14a10b", "type": "title", "text": [ "Paternal deletion 6q24.3: a new congenital anomaly syndrome associated with intrauterine growth failure, early developmental delay and characteristic facial appearance." ], "offsets": [ [ 0, 168 ] ] }, { "id": "dea5832b-5d78-4531-9d67-90916225d632", "type": "abstract", "text": [ "Deletions of the long arm of chromosome 6 are relatively uncommon and to date minimal genotype-phenotype correlations have been observed. We report on three unrelated patients with de novo paternal interstitial deletions of 6q24.3. FISH mapping was used to delineate the minimal region of overlap between these three patients. Although all three patients had different size deletions and different breakpoints, two of the patients shared a 2.5 Mb region of overlap and strikingly similar facial features including a triangular face, frontal bossing with metopic prominence, short and upward-slanting palpebral fissures, asymmetry of upper eyelids, hooded eyelids, shallow orbits, prominent inferior orbital crease, wide mouth, and long and flat philtrum. They also had redundant skin, joint laxity, a small thorax, and early developmental delay. The smallest region of overlap between all three patients was a region of deletion less than 1 Mb; all had a history of IUGR and postnatal short stature without overt radiologic skeletal anomalies. The dysmorphic features, early developmental and growth delay may be due to the hemizygous state for one of the genes in the deleted region of two of the patients or to a long range effect of the deletion on expression of other genes. In addition, since imprinted genes have been reported in this region, paternal deletion of an imprinted gene in all three patients may contribute to the growth phenotype. We propose that this is a new congenital malformation syndrome associated with a paternal deletion of 6q24.3." ], "offsets": [ [ 169, 1728 ] ] } ]

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[ { "id": "35472e30-ec77-4ce3-a0c5-63138b8ea7ea", "type": "title", "text": [ "A family with two consecutive nonsense mutations in BMPR1A causing juvenile polyposis." ], "offsets": [ [ 0, 86 ] ] }, { "id": "66e0250a-b9f8-45af-b538-f6f56d882582", "type": "abstract", "text": [ "We describe a novel germline mutation of BMPR1A in a family with juvenile polyposis and colon cancer. This mutation consists of two consecutive substitutions (735-6 TG>AT) that cause two nonsense mutations (Y245X, G246X), inherited in an autosomal dominant fashion, on one parental chromosome. This mutation caused protein truncation, and represents a novel case of consecutive nonsense mutations in human disease." ], "offsets": [ [ 87, 504 ] ] } ]

[ { "id": "78f83a44-b9b8-422c-8d32-ba7eaefa4b0a", "type": "Gene", "text": [ "BMPR1A" ], "offsets": [ [ 52, 58 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c1e54681-e09d-4990-be25-11f60a0a35d2", "type": "Gene", "text": [ "BMPR1A" ], "offsets": [ [ 128, 134 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "5012829a-951e-40b0-9409-da8a71de514b", "type": "title", "text": [ "The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency." ], "offsets": [ [ 0, 156 ] ] }, { "id": "2216321f-8814-4a0a-b2d0-40f10eadd8a9", "type": "abstract", "text": [ "BACKGROUND: Fumarate hydratase (HGNC approved gene symbol - FH), also known as fumarase, is an enzyme of the tricarboxylic acid (TCA) cycle, involved in fundamental cellular energy production. First described by Zinn et al in 1986, deficiency of FH results in early onset, severe encephalopathy. In 2002, the Multiple Leiomyoma Consortium identified heterozygous germline mutations of FH in patients with multiple cutaneous and uterine leiomyomas, (MCUL: OMIM 150800). In some families renal cell cancer also forms a component of the complex and as such has been described as hereditary leiomyomatosis and renal cell cancer (HLRCC: OMIM 605839). The identification of FH as a tumor suppressor was an unexpected finding and following the identification of subunits of succinate dehydrogenase in 2000 and 2001, was only the second description of the involvement of an enzyme of intermediary metabolism in tumorigenesis. DESCRIPTION: The FH mutation database is a part of the TCA cycle gene mutation database (formerly the succinate dehydrogenase gene mutation database) and is based on the Leiden Open (source) Variation Database (LOVD) system. The variants included in the database were derived from the published literature and annotated to conform to current mutation nomenclature. The FH database applies HGVS nomenclature guidelines, and will assist researchers in applying these guidelines when directly submitting new sequence variants online. Since the first molecular characterization of an FH mutation by Bourgeron et al in 1994, a series of reports of both FH deficiency patients and patients with MCUL/HLRRC have described 107 variants, of which 93 are thought to be pathogenic. The most common type of mutation is missense (57%), followed by frameshifts & nonsense (27%), and diverse deletions, insertions and duplications. Here we introduce an online database detailing all reported FH sequence variants. CONCLUSION: The FH mutation database strives to systematically unify all current genetic knowledge of FH variants. We believe that this knowledge will assist clinical geneticists and treating physicians when advising patients and their families, will provide a rapid and convenient resource for research scientists, and may eventually assist in gaining novel insights into FH and its related clinical syndromes." ], "offsets": [ [ 157, 2489 ] ] } ]

[ { "id": "632e7fd8-5e1a-48b4-93a7-39a4b0bef97f", "type": "Gene", "text": [ "FH" ], "offsets": [ [ 4, 6 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "932961d6-e56f-4876-8ca0-9b38f8e70100", "type": "Gene", "text": [ "fumarate hydratase" ], "offsets": [ [ 48, 66 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7e268a97-54c8-439c-a9b2-856764a141bb", "type": "Gene", "text": [ "fumarase" ], "offsets": [ [ 136, 144 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "98e09a59-a983-45da-886d-1bcd417810d5", "type": "Gene", "text": [ "Fumarate hydratase" ], "offsets": [ [ 169, 187 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e5ce78e3-6519-487a-a4e5-2ea3bd8da2c8", "type": "Gene", "text": [ "FH" ], "offsets": [ [ 217, 219 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d531a9f1-6062-4cef-a9d2-5516537e20c5", "type": "Gene", "text": [ "fumarase" ], "offsets": [ [ 236, 244 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "180f89ea-929e-4a0e-9a4b-49b994481656", "type": "Gene", "text": [ "FH" ], "offsets": [ [ 403, 405 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "449e5d70-33fb-4a22-b2ee-5c753985936f", "type": "Gene", "text": [ "FH" ], "offsets": [ [ 542, 544 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7bc21c9c-349f-4b3f-b9cf-7ac2d52ae4af", "type": "Gene", "text": [ "FH" ], "offsets": [ [ 825, 827 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a334549b-070d-4eb1-8b9e-b5b80fb3fa09", "type": "Gene", "text": [ "FH" ], "offsets": [ [ 1092, 1094 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1d9f60f5-09d0-4b87-9b5f-1b3b4c7f6415", "type": "Gene", "text": [ "FH" ], "offsets": [ [ 1444, 1446 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6e3550f0-7d11-4784-ad52-07b18f95fde4", "type": "Gene", "text": [ "FH" ], "offsets": [ [ 1655, 1657 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2b3ef155-88d2-4432-82bc-b446df6aae71", "type": "Gene", "text": [ "FH" ], "offsets": [ [ 1723, 1725 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0faaa469-724b-4983-bc2a-2d49dd294c1e", "type": "Gene", "text": [ "FH" ], "offsets": [ [ 2056, 2058 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9f1eed4f-d16c-40b3-9cf9-3aca14b441c5", "type": "Gene", "text": [ "FH" ], "offsets": [ [ 2094, 2096 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9a92dd32-cd78-4b2c-92bc-762330ab87d4", "type": "Gene", "text": [ "FH" ], "offsets": [ [ 2180, 2182 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5065d973-0ff3-4a97-a756-552f699d0ebf", "type": "Gene", "text": [ "FH" ], "offsets": [ [ 2451, 2453 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "0316c37e-5fbf-4a12-b45a-5c97bd139254", "type": "title", "text": [ "Genetic heterogeneity by comparative genomic hybridization in BRCAx breast cancers." ], "offsets": [ [ 0, 83 ] ] }, { "id": "2de53cb8-d135-433c-8665-0a9504943c6b", "type": "abstract", "text": [ "The chromosomal changes in eight familial BRCAx breast cancers (i.e., negative for BRCA1 or BRCA2) were analyzed by comparative genomic hybridization (CGH) to investigate intratumor heterogeneity. This was the first step in a study of most frequent chromosomal aberrations in BRCAx familial breast cancers. Laser microdissection analysis of paraffin tissue samples was followed by whole-genome amplification. CGH was performed on DNA isolated from two to three different cell groups per case to detect any cytogenetic aberrations in important clones that might have been missed when analyzing DNA extracted from large numbers of cells. The results were compared, to evaluate the influence of tumor heterogeneity on CGH, and the heterogeneity was confirmed comparing CGH with fluorescence in situ hybridization results. Different chromosomal aberrations were detected between adjacent clones within the same section, which highlights the utility of microdissection in addressing the problem of heterogeneity in whole-genome studies. Some chromosomal regions were more frequently altered in the eight BRCAx tumors; loss of 2q, 3p, 3q, 8p, 9p, and 15q and gains of 1p, 4p, 4q, 5p, 6q, 12q, and 19p were the most common. Further studies focusing on specific genes and sequences with more sensitive approaches, such as array-CGH, are warranted to confirm these findings." ], "offsets": [ [ 84, 1449 ] ] } ]

[ { "id": "cb850c30-f4c4-4f56-8ed6-88f6a8fe11ed", "type": "FamilyName", "text": [ "BRCAx" ], "offsets": [ [ 62, 67 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "55ac79ab-a550-408f-b8c7-738666e9e3ed", "type": "FamilyName", "text": [ "BRCAx" ], "offsets": [ [ 126, 131 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "318b0376-6a9c-47c7-b9d0-1312d23ef856", "type": "Gene", "text": [ "BRCA1" ], "offsets": [ [ 167, 172 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ee226d07-0a16-48e0-8825-cee2e274cec0", "type": "Gene", "text": [ "BRCA2" ], "offsets": [ [ 176, 181 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "211f19bd-ee2e-43ec-9081-0dbf7405a291", "type": "FamilyName", "text": [ "BRCAx" ], "offsets": [ [ 360, 365 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b7f238bd-0647-41d6-83a3-c772a8d5be6d", "type": "FamilyName", "text": [ "BRCAx" ], "offsets": [ [ 1183, 1188 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "3fd23a1c-12e6-4d08-99aa-cda5d52f8772", "type": "title", "text": [ "The infevers autoinflammatory mutation online registry: update with new genes and functions." ], "offsets": [ [ 0, 92 ] ] }, { "id": "d120852d-41c1-4582-80b9-f5796117641f", "type": "abstract", "text": [ "Infevers (Internet Fevers; http://fmf.igh.cnrs.fr/ISSAID/infevers), a website dedicated to mutations responsible for hereditary autoinflammatory diseases, was created in 2002 and has continued to evolve. This new version includes eight genes; six were already present: MEFV, MVK, TNFRSF1A, NLRP3, NOD2, PSTPIP1, and two are new, LPIN2 and NLRP7. Currently, Infevers contains over 540 sequence variants. Several new database functions were recently instituted. The website now accepts confidential data and complex alleles. For each gene, a newly created menu offers: 1) a tabular list of the variants that can be sorted by several parameters; 2) a gene graph providing a schematic representation of the variants along the gene; 3) statistical analysis of the data according to the phenotype, alteration type, and location of the mutation in the gene; 4) the cDNA and gDNA sequences of each gene, showing the nucleotide changes along the sequence, with a color-based code highlighting the gene domains, the first ATG, and the termination codon; and 5) a "download" menu making all tables and figures available for the users, which, except for the gene graphs, are all automatically generated and updated upon submission of the variants. Finally, the entire database was curated to comply with the HUGO Gene Nomenclature Committee (HGNC) and HGVS nomenclature guidelines, and wherever necessary, an informative note was provided. Infevers has already proven useful for the scientific community with a mean number of visits per month of 200 in 2002 and 800 in 2007, and its new design will lead to a more comprehensive comparative analysis and interpretation of auto-inflammatory sequence variants." ], "offsets": [ [ 93, 1798 ] ] } ]

[ { "id": "0b2e2b58-252d-4cdf-9f85-e6cba1f6fd9d", "type": "Gene", "text": [ "MEFV" ], "offsets": [ [ 362, 366 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c83a97d9-9c2a-453e-b4b5-1218bc1dfc33", "type": "Gene", "text": [ "MVK" ], "offsets": [ [ 368, 371 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9e8524f6-0ff1-4fb2-9d89-58932c30e759", "type": "Gene", "text": [ "TNFRSF1A" ], "offsets": [ [ 373, 381 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f9b2ed98-737a-4c90-a825-183ac100014c", "type": "Gene", "text": [ "NLRP3" ], "offsets": [ [ 383, 388 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "730b6984-90a5-4d8a-bd8d-aef9a6a377a0", "type": "Gene", "text": [ "NOD2" ], "offsets": [ [ 390, 394 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "dcb1bc00-9457-4c61-ba68-29d3f7977034", "type": "Gene", "text": [ "PSTPIP1" ], "offsets": [ [ 396, 403 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "22591090-6db8-42a9-969c-499a8a5a5fd7", "type": "Gene", "text": [ "LPIN2" ], "offsets": [ [ 422, 427 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c6bd33c0-33e0-4273-8e0a-d33ebf87023d", "type": "Gene", "text": [ "NLRP7" ], "offsets": [ [ 432, 437 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "36e98139-e111-4ae1-acf5-88a22053c79e", "type": "title", "text": [ "CYP2E1 polymorphisms and gene-environment interactions in the risk of upper aerodigestive tract cancers among Indians." ], "offsets": [ [ 0, 118 ] ] }, { "id": "593aa26a-667d-4056-8788-fdf3f2a5d38e", "type": "abstract", "text": [ "INTRODUCTION: The CYP2E1 enzyme is responsible for the metabolic activation of several procarcinogens into reactive metabolites that result in carcinogenesis. The genetic polymorphisms that modify these enzymatic activities may be associated with upper aerodigestive tract cancer risk. METHODS: This hospital-based study evaluated CYP2E1*1B, CYP2E1*5B and CYP2E1*6 polymorphisms in 408 histopathologically confirmed cases and 220 population-based controls using PCR-RFLP methods. RESULTS: The multivariate logistic regression analyses demonstrated no significant differences between groups for all three polymorphisms when analyzed separately. However, the gene-environment interactions analyses revealed significant interactions among tobacco smokers (11-20 pack years), 20-40 pack years and > 40 pack years), regular tobacco chewers and alcoholics carrying CYP2E1*1B mutant genotypes. Similarly, CYP2E1*6 polymorphisms resulted in significant interactions among tobacco smokers (> 40 pack years) and regular tobacco chewers on the multiplicative scale. CONCLUSION: The significant gene-environment interactions observed for CYP2E1*1B and CYP2E1*6 polymorphic genotypes may confer a substantial risk for upper aerodigestive tract cancers among Indians." ], "offsets": [ [ 119, 1378 ] ] } ]

[ { "id": "d27ba127-8566-482d-b2b1-eb27a1674079", "type": "Gene", "text": [ "CYP2E1" ], "offsets": [ [ 0, 6 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2051d0fa-25f2-4474-b8e5-e781301b2e2e", "type": "Gene", "text": [ "CYP2E1" ], "offsets": [ [ 137, 143 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "574b2451-57b4-43d9-8cc5-b1784d9b7950", "type": "Gene", "text": [ "CYP2E1" ], "offsets": [ [ 450, 456 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2a1107b8-154e-4723-bc2d-a586df762cb7", "type": "Gene", "text": [ "CYP2E1" ], "offsets": [ [ 461, 467 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e209a078-bc8a-43bb-b509-9618685cac39", "type": "Gene", "text": [ "CYP2E1" ], "offsets": [ [ 475, 481 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "97e30763-4311-4586-8f8e-6870e509b06a", "type": "Gene", "text": [ "CYP2E1" ], "offsets": [ [ 981, 987 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f2c06b34-2cb8-494c-a23c-db15eeba6a3f", "type": "Gene", "text": [ "CYP2E1" ], "offsets": [ [ 1020, 1026 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "af2f1c8d-e064-4b5d-a80e-dd0c917ef16a", "type": "Gene", "text": [ "CYP2E1" ], "offsets": [ [ 1251, 1257 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d2c2b215-d9f0-46e6-94bb-d1f00d6363eb", "type": "Gene", "text": [ "CYP2E1" ], "offsets": [ [ 1265, 1271 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "a22c0ac5-57a7-400e-9f7a-5f6c83414d7d", "type": "title", "text": [ "Depletion of mitochondrial DNA in fibroblast cultures from patients with POLG1 mutations is a consequence of catalytic mutations." ], "offsets": [ [ 0, 129 ] ] }, { "id": "e0f04ff4-cba1-4ad9-aac7-52ad68398b50", "type": "abstract", "text": [ "We investigated clinical and cellular phenotypes of 24 children with mutations in the catalytic (alpha) subunit of the mitochondrial DNA (mtDNA) gamma polymerase (POLG1). Twenty-one had Alpers syndrome, the commonest severe POLG1 autosomal recessive phenotype, comprising hepatoencephalopathy and often mtDNA depletion. The cellular mtDNA content reflected the genotype more closely than did clinical features. Patients with tissue depletion of mtDNA all had at least one allele with either a missense mutation in a catalytic domain or a nonsense mutation. Four out of 12 patients exhibited a progressive, mosaic pattern of mtDNA depletion in cultured fibroblasts. All these patients had mutations in a catalytic domain in both POLG1 alleles, in either the polymerase or exonuclease domain or both. The tissue mtDNA content of patients who had two linker mutations was normal, and their phenotypes the mildest. Epilepsy and/or movement disorder were major features in all 21. Previous studies have implicated replication stalling as a mechanism for mtDNA depletion. The mosaic cellular depletion that we have demonstrated in cell cultures may be a manifestation of severe replication stalling. One patient with a severe cellular and clinical phenotype was a compound heterozygote with POLG1 mutations in the polymerase and exonuclease domain intrans. This suggests that POLG1 requires both polymerase and 3'-5' exonuclease activity in the same molecule. This is consistent with current functional models for eukaryotic DNA polymerases, which alternate between polymerizing and editing modes, as determined by competition between these two active sites for the 3' end of the DNA." ], "offsets": [ [ 130, 1823 ] ] } ]

[ { "id": "9e5e741d-b875-4c34-8a09-e4abc189baa9", "type": "Gene", "text": [ "POLG1" ], "offsets": [ [ 73, 78 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7f7fa473-b5e0-40c9-96d3-42373e97df81", "type": "Gene", "text": [ "mitochondrial DNA (mtDNA) gamma polymerase" ], "offsets": [ [ 249, 291 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ed62f124-e163-4097-92f6-fd24ae51eba3", "type": "Gene", "text": [ "POLG1" ], "offsets": [ [ 293, 298 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0cfc5160-9c2d-4bc3-ad8c-fd663f9fcae0", "type": "Gene", "text": [ "POLG1" ], "offsets": [ [ 354, 359 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "580dae70-c41f-4f8c-9ea9-ec0d85a9e279", "type": "DomainMotif", "text": [ "catalytic domain" ], "offsets": [ [ 646, 662 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a7408cb6-4789-4e46-845a-185ee0f6a3ab", "type": "DomainMotif", "text": [ "catalytic domain" ], "offsets": [ [ 833, 849 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "415cbc0c-8be8-46d9-a50a-ec75b8249c61", "type": "Gene", "text": [ "POLG1" ], "offsets": [ [ 858, 863 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0f486149-8b45-4c83-86c5-4418ac353f95", "type": "Gene", "text": [ "POLG1" ], "offsets": [ [ 1415, 1420 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a1d9c93e-8d29-4792-a690-d4e7ddc1790b", "type": "Gene", "text": [ "POLG1" ], "offsets": [ [ 1500, 1505 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "942c5442-c081-41ac-819b-75bb2b8a72a2", "type": "title", "text": [ "Identification of novel dyslexia candidate genes through the analysis of a chromosomal deletion." ], "offsets": [ [ 0, 96 ] ] }, { "id": "021267ef-50d1-4756-bda5-4b61b302bcdf", "type": "abstract", "text": [ "Dyslexia is the most common childhood learning disorder and it is a significantly heritable trait. At least nine chromosomal loci have been linked to dyslexia, and additional susceptibility loci on other chromosomes have been suggested. Within two of these loci, DYX1C1 (15q21) and ROBO1 (3p12) have recently been proposed as dyslexia candidate genes through the molecular analysis of translocation breakpoints in dyslexic individuals carrying balanced chromosomal translocations. Moreover, genetic association studies have indicated a cluster of five dyslexia candidate genes in another linkage region on chromosome 6p22, although there is currently no consensus about which of these five genes contributes to the genetic susceptibility for dyslexia. In this article, we report the identification of four new dyslexia candidate genes (PCNT, DIP2A, S100B, and PRMT2) on chromosome region 21q22.3 by FISH and SNP microarray analyses of a very small deletion in this region, which cosegregates with dyslexia in a father and his three sons." ], "offsets": [ [ 97, 1134 ] ] } ]

[ { "id": "615e0ad3-41f5-4b6e-bab4-44cf5a9029d3", "type": "FamilyName", "text": [ "dyslexia candidate" ], "offsets": [ [ 24, 42 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "891e5155-94d7-4774-b607-8fff15a7b997", "type": "Gene", "text": [ "DYX1C1" ], "offsets": [ [ 360, 366 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d25bdee8-9c03-4e4b-bc41-241a58d776ad", "type": "Gene", "text": [ "ROBO1" ], "offsets": [ [ 379, 384 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "dc5f16b9-ea9a-4d23-8b89-1dfad0d3950c", "type": "FamilyName", "text": [ "dyslexia candidate" ], "offsets": [ [ 423, 441 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2f52f434-4099-4458-aa49-29ff8fade921", "type": "FamilyName", "text": [ "dyslexia candidate" ], "offsets": [ [ 649, 667 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4de8a3b7-40ec-42d9-a6b8-b29d92d431d2", "type": "FamilyName", "text": [ "dyslexia candidate" ], "offsets": [ [ 907, 925 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "28a0d57f-e56e-4c3d-92af-72047028e97e", "type": "Gene", "text": [ "PCNT" ], "offsets": [ [ 933, 937 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8490109d-cc02-46b0-83d9-946ced4910cf", "type": "Gene", "text": [ "DIP2A" ], "offsets": [ [ 939, 944 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "298033ba-9ee8-4d38-a1f8-17561300b5e2", "type": "Gene", "text": [ "S100B" ], "offsets": [ [ 946, 951 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9a2a8ba4-e730-4234-a6b7-0d60cc6829bc", "type": "Gene", "text": [ "PRMT2" ], "offsets": [ [ 957, 962 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "085672cf-24d1-4c7c-8a37-8ca2791ec379", "type": "title", "text": [ "Granulin mutations associated with frontotemporal lobar degeneration and related disorders: an update." ], "offsets": [ [ 0, 102 ] ] }, { "id": "27e55094-a175-43de-9803-2486c7bfba0e", "type": "abstract", "text": [ "Mutations in the gene encoding granulin (HUGO gene symbol GRN, also referred to as progranulin, PGRN), located at chromosome 17q21, were recently linked to tau-negative ubiquitin-positive frontotemporal lobar degeneration (FTLDU). Since then, 63 heterozygous mutations were identified in 163 families worldwide, all leading to loss of functional GRN, implicating a haploinsufficiency mechanism. Together, these mutations explained 5 to 10% of FTLD. The high mutation frequency, however, might still be an underestimation because not all patient samples were examined for all types of loss-of-function mutations and because several variants, including missense mutations, have a yet uncertain pathogenic significance. Although the complete phenotypic spectrum associated with GRN mutations is not yet fully characterized, it was shown that it is highly heterogeneous, suggesting the influence of modifying factors. A role of GRN in neuronal survival was suggested but the exact mechanism by which neurodegeneration and deposition of pathologic brain inclusions occur still has to be clarified." ], "offsets": [ [ 103, 1195 ] ] } ]

[ { "id": "b19c57b6-93d8-4a82-b14e-e02da9e9ed6e", "type": "Gene", "text": [ "Granulin" ], "offsets": [ [ 0, 8 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ba5f6ab0-d6c8-472f-b3e6-49287e52abc9", "type": "Gene", "text": [ "granulin" ], "offsets": [ [ 134, 142 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "39393000-b76e-4cf3-942b-c6a92779c76f", "type": "Gene", "text": [ "GRN" ], "offsets": [ [ 161, 164 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ae1d104f-4de8-4c7e-baee-3b147d9587c5", "type": "Gene", "text": [ "progranulin" ], "offsets": [ [ 186, 197 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "04a036e0-cf86-415f-972f-8ae639943e02", "type": "Gene", "text": [ "PGRN" ], "offsets": [ [ 199, 203 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8350dc3c-8423-487d-95c1-09f128ae7345", "type": "Gene", "text": [ "GRN" ], "offsets": [ [ 449, 452 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5ffb0742-600d-4680-9288-525a6f82cded", "type": "Gene", "text": [ "GRN" ], "offsets": [ [ 878, 881 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "843a489a-0545-4a82-8445-f856b86811f4", "type": "Gene", "text": [ "GRN" ], "offsets": [ [ 1027, 1030 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "e31ae5df-ac9d-476a-a65e-a6003c8e5d42", "type": "title", "text": [ "LDLR promoter variant and exon 14 mutation on the same chromosome are associated with an unusually severe FH phenotype and treatment resistance." ], "offsets": [ [ 0, 144 ] ] }, { "id": "67edeadc-d6b5-4ce9-94a4-97d4449ef136", "type": "abstract", "text": [ "Familial hypercholesterolemia (FH) is the most common form of autosomal-dominant hypercholesterolemia, and is caused by mutations in the low-density lipoprotein receptor (LDLR) gene. Heterozygous FH is characterized by elevated low-density lipoprotein (LDL) cholesterol and early-onset cardiovascular disease, whereas homozygous FH results in more severe LDL cholesterol elevation with death by 20 years of age. We present here the case of an African-American female FH patient presenting with a myocardial infarction at the age of 48, recurrent angina pectoris and numerous coronary artery stents. Her pretreated LDL cholesterol levels were more typical of a homozygous FH pattern and she was resistant to conventional lipid-lowering treatment, yet her other clinical parameters were not necessarily consistent with homozygous FH. Genetic testing revealed two LDLR variants on the same chromosome: one a novel missense mutation in exon 14 (Cys681Gly) and the other a promoter variant (IVS1-217C>T) previously shown to result in increased LDLR transcription. Disease-associated PCSK9 or APOB mutations were not identified in this individual. Overall, her genetic and clinical profile suggests that enhanced expression of the mutant LDLR allele resulted in a severe phenotype with characteristics of both heterozygous and homozygous FH." ], "offsets": [ [ 145, 1483 ] ] } ]

[ { "id": "98c1d3af-5cdb-47cf-80d2-324d779b401a", "type": "Gene", "text": [ "LDLR" ], "offsets": [ [ 0, 4 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e522a602-f7ad-4a17-9e31-74a08f2539a7", "type": "Gene", "text": [ "low-density lipoprotein receptor" ], "offsets": [ [ 282, 314 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8059b8af-ff09-4f2e-8606-a152fbae315b", "type": "Gene", "text": [ "LDLR" ], "offsets": [ [ 316, 320 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f5bb8148-b8cc-440e-a745-c8310bed0846", "type": "FamilyName", "text": [ "low-density lipoprotein" ], "offsets": [ [ 373, 396 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "88e1a9d4-3d62-4252-af5b-3831d027a4f6", "type": "FamilyName", "text": [ "LDL" ], "offsets": [ [ 398, 401 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "31d8cc8b-3e4f-4179-9b11-8cd360a6096b", "type": "FamilyName", "text": [ "LDL" ], "offsets": [ [ 500, 503 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cb8822af-a1c6-4df5-8210-d3abfa06c1de", "type": "FamilyName", "text": [ "LDL" ], "offsets": [ [ 759, 762 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "86188e17-82b7-4e27-b044-2f2ac6664738", "type": "Gene", "text": [ "LDLR" ], "offsets": [ [ 1006, 1010 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9f22a7a0-8e25-4c11-980f-b95f5fad8aad", "type": "Gene", "text": [ "LDLR" ], "offsets": [ [ 1187, 1191 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c1b7b79f-9174-4e8c-8013-d523b7ea48a7", "type": "Gene", "text": [ "PCSK9" ], "offsets": [ [ 1226, 1231 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e320f0ec-25ae-4096-9057-353d6c5e7e31", "type": "Gene", "text": [ "APOB" ], "offsets": [ [ 1235, 1239 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d5b6d327-3fd3-4e30-b718-3be2bd982366", "type": "Gene", "text": [ "LDLR" ], "offsets": [ [ 1380, 1384 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "0d8ff553-e1f8-4d6b-bd9c-c985b01f777a", "type": "title", "text": [ "Novel suppressors of alpha-synuclein toxicity identified using yeast." ], "offsets": [ [ 0, 69 ] ] }, { "id": "2f382782-bdc1-468f-9187-7d27bb508412", "type": "abstract", "text": [ "The mechanism by which the Parkinson's disease-related protein alpha-synuclein (alpha-syn) causes neurodegeneration has not been elucidated. To determine the genes that protect cells from alpha-syn, we used a genetic screen to identify suppressors of the super sensitivity of the yeast Saccharomyces cerevisiae expressing alpha-syn to killing by hydrogen peroxide. Forty genes in ubiquitin-dependent protein catabolism, protein biosynthesis, vesicle trafficking and the response to stress were identified. Five of the forty genes--ENT3, IDP3, JEM1, ARG2 and HSP82--ranked highest in their ability to block alpha-syn-induced reactive oxygen species accumulation, and these five genes were characterized in more detail. The deletion of any of these five genes enhanced the toxicity of alpha-syn as judged by growth defects compared with wild-type cells expressing alpha-syn, which indicates that these genes protect cells from alpha-syn. Strikingly, four of the five genes are specific for alpha-syn in that they fail to protect cells from the toxicity of the two inherited mutants A30P or A53T. This finding suggests that alpha-syn causes toxicity to cells through a different pathway than these two inherited mutants. Lastly, overexpression of Ent3p, which is a clathrin adapter protein involved in protein transport between the Golgi and the vacuole, causes alpha-syn to redistribute from the plasma membrane into cytoplasmic vesicular structures. Our interpretation is that Ent3p mediates the transport of alpha-syn to the vacuole for proteolytic degradation. A similar clathrin adaptor protein, epsinR, exists in humans." ], "offsets": [ [ 70, 1698 ] ] } ]

[ { "id": "17d24664-90dc-4f5e-be7c-92ece4cc2401", "type": "Gene", "text": [ "alpha-synuclein" ], "offsets": [ [ 21, 36 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "47ea02cc-bbfa-4093-9f3e-4f01010ec010", "type": "Gene", "text": [ "alpha-synuclein" ], "offsets": [ [ 138, 153 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d6c5c2d6-8c96-418b-a2d6-7fd4e487dba2", "type": "Gene", "text": [ "alpha-syn" ], "offsets": [ [ 155, 164 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8e5c76a5-a344-4ec7-9e91-afd68d7927cf", "type": "Gene", "text": [ "alpha-syn" ], "offsets": [ [ 263, 272 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "728d27cb-a664-47a5-a60a-d7a1e788e230", "type": "Gene", "text": [ "alpha-syn" ], "offsets": [ [ 397, 406 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d71736b9-cf62-46c8-bdf3-ea94bf831af2", "type": "Gene", "text": [ "ENT3" ], "offsets": [ [ 606, 610 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d7b5a62b-2266-48d6-9f61-4b4a3ed39582", "type": "Gene", "text": [ "IDP3" ], "offsets": [ [ 612, 616 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f83b6e28-4770-4e9b-808a-e7e59b5a245d", "type": "Gene", "text": [ "JEM1" ], "offsets": [ [ 618, 622 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8b19b616-e2d2-4d90-972a-109d6be5c356", "type": "Gene", "text": [ "ARG2" ], "offsets": [ [ 624, 628 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f5f441f7-b264-4d89-a9ca-3a0f9a150a16", "type": "Gene", "text": [ "HSP82" ], "offsets": [ [ 633, 638 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "08eaa6b8-9cbf-4032-ad3d-2a73b69462f6", "type": "Gene", "text": [ "alpha-syn" ], "offsets": [ [ 681, 690 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "aed6b516-9e28-45e6-bd79-8a1879e357c6", "type": "Gene", "text": [ "alpha-syn" ], "offsets": [ [ 858, 867 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d2ce09dc-dcf8-4d56-84bb-d1b1fa1cbe8a", "type": "Gene", "text": [ "alpha-syn" ], "offsets": [ [ 937, 946 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cbd374b6-7fd7-44a1-9ae6-bbd84313d88b", "type": "Gene", "text": [ "alpha-syn" ], "offsets": [ [ 1000, 1009 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c8d90151-435c-4d4c-9dfa-dd7355f7d34a", "type": "Gene", "text": [ "alpha-syn" ], "offsets": [ [ 1063, 1072 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c09dbb09-2f46-45e6-9ca4-3dde38aa0f32", "type": "Gene", "text": [ "alpha-syn" ], "offsets": [ [ 1196, 1205 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "93619b13-894a-419d-83e6-dc3a264205c0", "type": "Gene", "text": [ "Ent3p" ], "offsets": [ [ 1319, 1324 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6dadf121-8b2f-458d-9f2d-ac6bd931b189", "type": "FamilyName", "text": [ "Golgi" ], "offsets": [ [ 1404, 1409 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c06e5dc2-1f62-49db-a012-df2f078a25af", "type": "Gene", "text": [ "alpha-syn" ], "offsets": [ [ 1434, 1443 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "38e1a613-677e-4740-b23d-1edb3374a435", "type": "Gene", "text": [ "Ent3p" ], "offsets": [ [ 1551, 1556 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "57ef611d-f66b-4dff-b0e1-787402c8ef37", "type": "Gene", "text": [ "alpha-syn" ], "offsets": [ [ 1583, 1592 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "71d00874-cb3a-4994-bcac-bbdd2d6c6adc", "type": "Gene", "text": [ "epsinR" ], "offsets": [ [ 1673, 1679 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "2b77e10b-0227-4c90-9f41-c32e44034121", "type": "title", "text": [ "Polymorphism of the hepatic influx transporter organic anion transporting polypeptide 1B1 is associated with increased cholesterol synthesis rate." ], "offsets": [ [ 0, 146 ] ] }, { "id": "425f11de-1f56-4a76-8204-4d88da74f128", "type": "abstract", "text": [ "We investigated the influence of SLCO1B1 polymorphism on cholesterol synthesis and absorption during baseline, and as affected by statins. In a crossover study, 32 healthy volunteers with different SLCO1B1 genotypes ingested a single dose of fluvastatin, pravastatin, simvastatin, rosuvastatin, and atorvastatin. Plasma total cholesterol, and cholesterol synthesis and absorption markers were measured before statin administration and up to 12 h thereafter. The mean fasting baseline plasma desmosterol to cholesterol ratio was 40% higher in participants with the SLCO1B1 c.521CC variant genotype than in those with the c.521TT genotype (P=0.043). The genotype had no significant effect on cholesterol absorption markers. All statins decreased lathosterol and avenasterol to cholesterol ratios, but no significant differences in the response existed between SLCO1B1 genotypes. In conclusion, the low activity SLCO1B1 c.521CC genotype is associated with an increased cholesterol synthesis rate. The short-term effects of statins on cholesterol homeostasis were not associated with the SLCO1B1 polymorphism." ], "offsets": [ [ 147, 1252 ] ] } ]

[ { "id": "616fbf20-8dcb-40dc-8d66-32ff1eb21c25", "type": "Gene", "text": [ "hepatic influx transporter organic anion transporting polypeptide 1B1" ], "offsets": [ [ 20, 89 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4b29ade5-966a-4789-8ae9-3ba771c3319d", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 180, 187 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d339f218-bbc6-4e1d-8dad-4ab7b323794e", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 345, 352 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cb665061-d550-444c-9f4a-3885303fa1c2", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 711, 718 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ad9c8872-3968-4847-a4b2-2a2679117c29", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 1005, 1012 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4cd0e73b-bc85-4a8e-91c5-b3143a926414", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 1056, 1063 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "67f76972-7edf-4669-a6e9-68520efbe5a1", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 1231, 1238 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "fc865e98-0fc9-413c-9a3f-3c4295bb355c", "type": "title", "text": [ "Association of a null allele of SPRN with variant Creutzfeldt-Jakob disease." ], "offsets": [ [ 0, 76 ] ] }, { "id": "d3ae1820-648a-40d7-a4a5-b6a492566a9c", "type": "abstract", "text": [ "BACKGROUND: No susceptibility genes have been identified in human prion disase, apart from the prion protein gene (PRNP). The gene SPRN, encodes Shadoo (Sho, shadow of prion protein) which has protein homology and possible functional links with the prion protein. METHODS: A genetic screen was carried out of the open reading frame of SPRN by direct sequencing in 522 patients with prion disease, including 107 with variant Creutzfeldt-Jakob disease (vCJD), and 861 healthy controls. RESULTS: A common coding variant of SPRN, two further single nucleotide polymorphisms (SNPs) and three rare insertion or deletion variants were found. A single base-pair insertion at codon 46, predicted to cause a frameshift and potentially a novel protein, was found in two patients with vCJD but not in controls (p = 0.01). Two linked SNPs, one in intron 1 and the other a missense variant at codon 7, were associated with risk of sporadic CJD (p = 0.009). CONCLUSION: These data justify the functional genetic characterisation of SPRN and support the involvement of Shadoo in prion pathobiology." ], "offsets": [ [ 77, 1159 ] ] } ]

[ { "id": "9231a9a1-3e23-4d07-a75a-06799c504b20", "type": "Gene", "text": [ "SPRN" ], "offsets": [ [ 32, 36 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "612ac1c6-cf7d-4c84-af52-4a8ecf5b3df1", "type": "Gene", "text": [ "prion protein" ], "offsets": [ [ 172, 185 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e84affb6-05b1-40c0-bbf8-5db2528029ff", "type": "Gene", "text": [ "PRNP" ], "offsets": [ [ 192, 196 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1fae2030-1250-413d-bd76-58e8c7ea4289", "type": "Gene", "text": [ "SPRN" ], "offsets": [ [ 208, 212 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "285451e9-d5d4-44b2-8a53-3a05a2c83b52", "type": "Gene", "text": [ "Shadoo" ], "offsets": [ [ 222, 228 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b68da8e7-cede-40e8-be33-2ccbb4915611", "type": "Gene", "text": [ "Sho" ], "offsets": [ [ 230, 233 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0785fe04-e0b0-4fa9-bc16-8d7254450c73", "type": "Gene", "text": [ "shadow of prion protein" ], "offsets": [ [ 235, 258 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e7be9d49-76e6-4b92-923c-97288836c1d4", "type": "Gene", "text": [ "prion protein" ], "offsets": [ [ 326, 339 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f27d96db-1387-4f11-a391-201987eacced", "type": "Gene", "text": [ "SPRN" ], "offsets": [ [ 412, 416 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "662d9670-eda1-481d-8a87-be8babab2625", "type": "Gene", "text": [ "SPRN" ], "offsets": [ [ 597, 601 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d96550ba-a990-4a26-bd51-eb4d74769242", "type": "Gene", "text": [ "SPRN" ], "offsets": [ [ 1094, 1098 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "61ebe697-88df-4ae7-b4ba-ae589f25711d", "type": "Gene", "text": [ "Shadoo" ], "offsets": [ [ 1130, 1136 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "8bb54039-10e8-4e0a-9abe-62029f4527cf", "type": "title", "text": [ "Locus-specific databases and recommendations to strengthen their contribution to the classification of variants in cancer susceptibility genes." ], "offsets": [ [ 0, 143 ] ] }, { "id": "f4d0c79c-e78a-492a-b93b-c66fb3cd0576", "type": "abstract", "text": [ "Locus-specific databases (LSDBs) are curated collections of sequence variants in genes associated with disease. LSDBs of cancer-related genes often serve as a critical resource to researchers, diagnostic laboratories, clinicians, and others in the cancer genetics community. LSDBs are poised to play an important role in disseminating clinical classification of variants. The IARC Working Group on Unclassified Genetic Variants has proposed a new system of five classes of variants in cancer susceptibility genes. However, standards are lacking for reporting and analyzing the multiple data types that assist in classifying variants. By adhering to standards of transparency and consistency in the curation and annotation of data, LSDBs can be critical for organizing our understanding of how genetic variation relates to disease. In this article we discuss how LSDBs can accomplish these goals, using existing databases for BRCA1, BRCA2, MSH2, MLH1, TP53, and CDKN2A to illustrate the progress and remaining challenges in this field. We recommend that: 1) LSDBs should only report a conclusion related to pathogenicity if a consensus has been reached by an expert panel. 2) The system used to classify variants should be standardized. The Working Group encourages use of the five class system described in this issue by Plon and colleagues. 3) Evidence that supports a conclusion should be reported in the database, including sources and criteria used for assignment. 4) Variants should only be classified as pathogenic if more than one type of evidence has been considered. 5) All instances of all variants should be recorded." ], "offsets": [ [ 144, 1772 ] ] } ]

[ { "id": "9ce113c7-96cd-47b3-ba2d-6d6f404e7c52", "type": "FamilyName", "text": [ "cancer susceptibility genes" ], "offsets": [ [ 115, 142 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ace11be6-e7ba-4f29-8b6f-8d069e84dce8", "type": "FamilyName", "text": [ "cancer-related genes" ], "offsets": [ [ 265, 285 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b80a3a5b-ed47-407e-8139-2a405b82e527", "type": "Gene", "text": [ "BRCA1" ], "offsets": [ [ 1069, 1074 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "673149ca-356c-470a-aab3-55ffd8ff8546", "type": "Gene", "text": [ "BRCA2" ], "offsets": [ [ 1076, 1081 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c3881369-dcbf-4965-98b6-06055e33a3db", "type": "Gene", "text": [ "MSH2" ], "offsets": [ [ 1083, 1087 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "457c21e5-dc86-47ac-a9fa-52f4422ccce3", "type": "Gene", "text": [ "MLH1" ], "offsets": [ [ 1089, 1093 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b9602bfc-2fd0-4b96-ac6c-b850c6d4519d", "type": "Gene", "text": [ "TP53" ], "offsets": [ [ 1095, 1099 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e970e349-b3bf-459c-b693-7e2da318ab64", "type": "Gene", "text": [ "CDKN2A" ], "offsets": [ [ 1105, 1111 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "5db979ec-64d7-41a6-8043-093a06c3fb6f", "type": "title", "text": [ "Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population." ], "offsets": [ [ 0, 141 ] ] }, { "id": "5ecc949e-583b-41db-a928-dd4399f5d7ae", "type": "abstract", "text": [ "According to recent genome-wide association studies, a number of single nucleotide polymorphisms (SNPs) are reported to be associated with type 2 diabetes mellitus (T2DM). The aim of the present study was to investigate the association among the polymorphisms of SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1 and KCNQ1 and the risk of T2DM in the Korean population. This study was based on a multicenter case-control study, including 908 patients with T2DM and 502 non-diabetic controls. We genotyped rs13266634, rs1111875, rs10811661, rs4402960, rs8050136, rs734312, rs7754840 and rs2237892 and measured the body weight, body mass index and fasting plasma glucose in all patients and controls. The strongest association was found in a variant of CDKAL1 [rs7754840, odds ratio (OR) = 1.77, 95% CI = 1.50-2.10, p = 5.0 x 10(-11)]. The G allele of rs1111875 (OR = 1.43, 95% CI = 1.18-1.72, p = 1.8 x 10(-4)) in HHEX), the T allele of rs10811661 (OR = 1.47, 95% CI = 1.23-1.75, p = 2.1 x 10(-5)) in CDKN2A/B) and the C allele of rs2237892 (OR = 1.31, 95% CI = 1.10-1.56, p = 0.003) in KCNQ1 showed significant associations with T2DM. Rs13266634 (OR = 1.19, 95% CI = 1.00-1.42, p = 0.045) in SLC30A8 showed a nominal association with the risk of T2DM, whereas SNPs in IGF2BP2, FTO and WFS1 were not associated. In conclusion, we have shown that SNPs in HHEX, CDKN2A/B, CDKAL1, KCNQ1 and SLC30A8 confer a risk of T2DM in the Korean population." ], "offsets": [ [ 142, 1586 ] ] } ]

[ { "id": "8904980d-6643-4692-9f2c-d1f5bf50e474", "type": "Gene", "text": [ "SLC30A8" ], "offsets": [ [ 37, 44 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f4449230-103e-420d-a50c-4601931e6492", "type": "Gene", "text": [ "HHEX" ], "offsets": [ [ 46, 50 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6dfab016-fdf9-440d-a35d-461638444828", "type": "Gene", "text": [ "CDKN2A/B" ], "offsets": [ [ 52, 60 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6f82dfec-1ab4-44ab-b7b9-df7583ba2262", "type": "Gene", "text": [ "IGF2BP2" ], "offsets": [ [ 62, 69 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1d63c2fb-49a9-485f-9d27-854078ed7528", "type": "Gene", "text": [ "FTO" ], "offsets": [ [ 71, 74 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2874491e-87d8-4127-9cfb-66800833a3ba", "type": "Gene", "text": [ "WFS1" ], "offsets": [ [ 76, 80 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "974547d2-453e-4820-adb3-fadd8d878ebc", "type": "Gene", "text": [ "CDKAL1" ], "offsets": [ [ 82, 88 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "54ec6cc2-4cd7-4dea-a185-5018a99252b5", "type": "Gene", "text": [ "KCNQ1" ], "offsets": [ [ 90, 95 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "624ec31e-ffd4-4770-aa40-6154517d716a", "type": "Gene", "text": [ "SLC30A8" ], "offsets": [ [ 405, 412 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e1e60843-cf4d-40d0-ae3c-9dd0ac1171aa", "type": "Gene", "text": [ "HHEX" ], "offsets": [ [ 414, 418 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "333a6cc7-8524-4018-a394-fe9f2da64437", "type": "Gene", "text": [ "CDKN2A/B" ], "offsets": [ [ 420, 428 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ba06db8e-eec7-4949-8630-a3eb2b555781", "type": "Gene", "text": [ "IGF2BP2" ], "offsets": [ [ 430, 437 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7efa774f-00ff-455b-9d65-9d73ebb3eaa2", "type": "Gene", "text": [ "FTO" ], "offsets": [ [ 439, 442 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "990c0778-a741-44f2-8ac5-7645dde597e4", "type": "Gene", "text": [ "WFS1" ], "offsets": [ [ 444, 448 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8fb113b2-6923-4a14-95ba-e46c0f666220", "type": "Gene", "text": [ "CDKAL1" ], "offsets": [ [ 450, 456 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "bad44d28-db79-4130-9ef9-da278772d552", "type": "Gene", "text": [ "KCNQ1" ], "offsets": [ [ 461, 466 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f1ee20ff-55a9-419f-9b1d-d1d373036e51", "type": "Gene", "text": [ "CDKAL1" ], "offsets": [ [ 895, 901 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0c2d197c-1a28-4132-bbb6-d4c140cf5322", "type": "Gene", "text": [ "HHEX" ], "offsets": [ [ 1057, 1061 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a8b2cf5a-5798-40a9-b8ad-7d6d195086dc", "type": "Gene", "text": [ "CDKN2A/B" ], "offsets": [ [ 1144, 1152 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "bbc97afe-09e4-418b-8ed3-456157e40b38", "type": "Gene", "text": [ "KCNQ1" ], "offsets": [ [ 1230, 1235 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "53c26616-ed91-4319-8d4e-1b39e6e3b98a", "type": "Gene", "text": [ "SLC30A8" ], "offsets": [ [ 1336, 1343 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7a9f39e5-2617-4190-ac29-710b007c2394", "type": "Gene", "text": [ "IGF2BP2" ], "offsets": [ [ 1412, 1419 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c9ab9c8f-5185-4f15-ad20-cd2606890e11", "type": "Gene", "text": [ "FTO" ], "offsets": [ [ 1421, 1424 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "dc55c065-5c7a-4e47-baf7-9308059b0d27", "type": "Gene", "text": [ "WFS1" ], "offsets": [ [ 1429, 1433 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "beb55978-1006-4b56-a067-38e964593232", "type": "Gene", "text": [ "HHEX" ], "offsets": [ [ 1497, 1501 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5692eb17-3221-4676-a668-f58ddbb85283", "type": "Gene", "text": [ "CDKN2A/B" ], "offsets": [ [ 1503, 1511 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e70b30db-0b24-45bb-8106-94cb9f498906", "type": "Gene", "text": [ "CDKAL1" ], "offsets": [ [ 1513, 1519 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1027df06-c154-40b5-bd9f-55cdf5024a89", "type": "Gene", "text": [ "KCNQ1" ], "offsets": [ [ 1521, 1526 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cc97d12a-4005-4c1f-8c59-fd82c7b92085", "type": "Gene", "text": [ "SLC30A8" ], "offsets": [ [ 1531, 1538 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "2476b265-262c-4a64-815a-14289dbc2637", "type": "title", "text": [ "Clinical practice and genetic counseling for cystic fibrosis and CFTR-related disorders." ], "offsets": [ [ 0, 88 ] ] }, { "id": "5a13a52f-f3fc-46cf-8d3a-37c13ad6eba3", "type": "abstract", "text": [ "Cystic fibrosis transmembrane conductance regulator-related disorders encompass a disease spectrum from focal male reproductive tract involvement in congenital absence of the vas deferens to multiorgan involvement in classic cystic fibrosis. The reproductive, gastrointestinal, and exocrine manifestations of cystic fibrosis transmembrane conductance regulator deficiency are correlated with CFTR genotype, whereas the respiratory manifestations that are the main cause of morbidity and mortality in cystic fibrosis are less predictable. Molecular genetic testing of CFTR has led to new diagnostic strategies and will enable targeting of molecular therapies now in development. Older diagnostic methods that measure sweat chloride and nasal potential difference nonetheless remain important because of their sensitivity and specificity. In addition, the measurement of immunoreactive trypsinogen and the genotyping of CFTR alleles are key to newborn screening programs because of low cost. The multiorgan nature of cystic fibrosis leads to a heavy burden of care, thus therapeutic regimens are tailored to the specific manifestations present in each patient. The variability of cystic fibrosis lung disease and the variable expressivity of mild CFTR alleles complicate genetic counseling for this autosomal recessive disorder. Widespread implementation of newborn screening programs among populations with significant cystic fibrosis mutation carrier frequencies is expected to result in increasing demands on genetic counseling resources." ], "offsets": [ [ 89, 1628 ] ] } ]

[ { "id": "d047bb8d-5f42-4325-973e-6904104a31e4", "type": "FamilyName", "text": [ "cystic fibrosis" ], "offsets": [ [ 45, 60 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5f56ecea-ee25-4564-ba78-7c8d1d7f7262", "type": "Gene", "text": [ "CFTR" ], "offsets": [ [ 65, 69 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c5b905e9-316b-49a2-821f-f5a5281407a7", "type": "Gene", "text": [ "Cystic fibrosis transmembrane conductance regulator" ], "offsets": [ [ 89, 140 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4b9058c5-3aea-4dea-808c-d0b638939d2c", "type": "FamilyName", "text": [ "cystic fibrosis" ], "offsets": [ [ 314, 329 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "08ac9de8-3c76-467a-be9c-b062963d511e", "type": "Gene", "text": [ "cystic fibrosis transmembrane conductance regulator" ], "offsets": [ [ 398, 449 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "30ee79d0-0de7-4269-9988-09fe6181df53", "type": "Gene", "text": [ "CFTR" ], "offsets": [ [ 481, 485 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "058a3590-52c0-4658-852d-d520803069d0", "type": "FamilyName", "text": [ "cystic fibrosis" ], "offsets": [ [ 589, 604 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1cba3c13-c2cb-4830-841e-f22b7890adf5", "type": "Gene", "text": [ "CFTR" ], "offsets": [ [ 656, 660 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6b136e15-8aae-4cd0-8283-40c99fd8019a", "type": "Gene", "text": [ "CFTR" ], "offsets": [ [ 1007, 1011 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e65b395d-7be4-4d58-9532-f94b6c37bbf3", "type": "FamilyName", "text": [ "cystic fibrosis" ], "offsets": [ [ 1104, 1119 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3fab01ba-83ec-4010-90cb-b2aa6dddd61d", "type": "FamilyName", "text": [ "cystic fibrosis" ], "offsets": [ [ 1267, 1282 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1ad1f185-068e-43df-9b9f-83d6852a058e", "type": "Gene", "text": [ "CFTR" ], "offsets": [ [ 1334, 1338 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "72caf015-af1c-4053-82d0-438d24433b92", "type": "FamilyName", "text": [ "cystic fibrosis" ], "offsets": [ [ 1507, 1522 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "cb15fd6b-1d90-4342-bf38-4b7f507c0bce", "type": "title", "text": [ "Breakpoint mapping and haplotype analysis of three reciprocal translocations identify a novel recurrent translocation in two unrelated families: t(4;11)(p16.2;p15.4)." ], "offsets": [ [ 0, 166 ] ] }, { "id": "f13bdb92-71e5-4b6b-a47b-e1535f841f0b", "type": "abstract", "text": [ "The majority of constitutional reciprocal translocations appear to be unique rearrangements arising from independent events. However, a small number of translocations are recurrent, most significantly the t(11;22)(q23;q11). Among large series of translocations there may be multiple independently ascertained cases with the same cytogenetic breakpoints. Some of these could represent additional recurrent rearrangements, alternatively they could be identical by descent (IBD) or have subtly different breakpoints when examined under higher resolution. We have used molecular breakpoint mapping and haplotyping to determine the origin of three pairs of reciprocal constitutional translocations, each with the same cytogenetic breakpoints. FISH mapping showed one pair to have different breakpoints and thus to be distinct rearrangements. Another pair of translocations were IBD with identical breakpoint intervals and highly conserved haplotypes on the derived chromosomes. The third pair, t(4;11)(p16.2;p15.4), had the same breakpoint intervals by aCGH and fosmid mapping but had very different haplotypes, therefore they represent a novel recurrent translocation. Unlike the t(11;22)(q23;q11), the formation of the t(4;11)(p16.2;p15.4) may have involved segmental duplications and sequence homology at the breakpoints. Additional examples of recurrent translocations could be identified if the resources were available to study more translocations using the approaches described here. However, like the t(4;11)(p16.2;p15.4), such translocations are likely to be rare with the t(11;22) remaining the only common recurrent constitutional reciprocal translocation." ], "offsets": [ [ 167, 1829 ] ] } ]

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[ { "id": "ee6b969e-5160-4f53-b25d-c136142cb5f2", "type": "title", "text": [ "Alterations of ROBO1/DUTT1 and ROBO2 loci in early dysplastic lesions of head and neck: clinical and prognostic implications." ], "offsets": [ [ 0, 125 ] ] }, { "id": "630b5d3e-8cd4-4d1f-b9ba-ba46b660cb05", "type": "abstract", "text": [ "Deletion of chromosomal 3p12.3 was suggested to be associated with dysplastic lesions of head and neck. This region harbors two candidate tumor suppressors ROBO1/DUTT1, ROBO2 and two non-coding RNAs (ncRNAs) located at intron 2 of ROBO1/DUTT1. Aim of this study is to understand the role of these genes in development of head and neck squamous cell carcinoma. A collection of 72 dysplastic lesions and 116 HNSCC samples and two oral cancer cell lines were analyzed for ROBO1/DUTT1 and ROBO2 deletion and promoter methylation. ROBO1/DUTT1, ROBO2 and two ncRNAs mRNA expression were analyzed by Q-PCR. Immunohistochemical analysis of ROBO1/DUTT1 and ROBO2 was performed. Alterations of these genes were correlated with different clinicopathological parameters. High frequency of molecular alterations (deletion/methylation) was seen in ROBO1/DUTT1 than ROBO2. In mild dysplastic lesions both of these genes showed high molecular alterations and remained more or less constant in subsequent stages. Q-PCR analysis showed reduced expression of these genes and the two ncRNAs. In vitro demethylation experiment by 5-aza-dC showed upregulation of ROBO1/DUTT1 and ROBO2 while the expression of the ncRNAs remained unchanged. Immunohistochemical analysis of ROBO1/DUTT1 and ROBO2 showed concordance with their mRNA expression and molecular alterations. Poor patients' outcome was predicted in the cases with alteration of ROBO1/DUTT1 along with tobacco addiction and nodal involvement. Our data suggests (a) ROBO1/DUTT1 and the ncRNAs are transcribed from different promoters, and (b) inactivation of ROBO1/DUTT1 could be used as molecular signature for early detection and prognosis of the head and neck cancer." ], "offsets": [ [ 126, 1835 ] ] } ]

[ { "id": "d230a93d-50cb-473e-8d61-b9e6e7473c6f", "type": "Gene", "text": [ "ROBO1" ], "offsets": [ [ 15, 20 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d21b9ab1-8f49-49d1-9a73-16c71b4ff21f", "type": "Gene", "text": [ "DUTT1" ], "offsets": [ [ 21, 26 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "41652d06-7326-42e2-895a-508909e5dfa5", "type": "Gene", "text": [ "ROBO2" ], "offsets": [ [ 31, 36 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "20c69eda-3c8c-4000-bbae-29a746ee3565", "type": "FamilyName", "text": [ "tumor suppressors" ], "offsets": [ [ 264, 281 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "362647a3-8d81-4297-80f3-6a0a2e0713ac", "type": "Gene", "text": [ "ROBO1" ], "offsets": [ [ 282, 287 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7bec2520-e882-4216-82bd-32fd4bd76ded", "type": "Gene", "text": [ "DUTT1" ], "offsets": [ [ 288, 293 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "826671cc-361a-4c9a-b472-8452600301b1", "type": "Gene", "text": [ "ROBO2" ], "offsets": [ [ 295, 300 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "84b30811-4e10-45b8-813b-61029edab16d", "type": "Gene", "text": [ "ROBO1" ], "offsets": [ [ 357, 362 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "59560c0e-e2e8-4e65-8480-c838f000afaf", "type": "Gene", "text": [ "DUTT1" ], "offsets": [ [ 363, 368 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4a4393df-913f-4ef4-a4fe-6e415bf184a9", "type": "Gene", "text": [ "ROBO1" ], "offsets": [ [ 595, 600 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fcf1a9cf-b74e-4ab6-a9bc-dc8a10b73421", "type": "Gene", "text": [ "DUTT1" ], "offsets": [ [ 601, 606 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "89bccedc-e782-4aec-8361-b7ec1710b9ac", "type": "Gene", "text": [ "ROBO2" ], "offsets": [ [ 611, 616 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e9c1e0e8-5082-4288-9e1b-32f1734d3740", "type": "Gene", "text": [ "ROBO1" ], "offsets": [ [ 652, 657 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "38f76c36-507c-439d-97c5-c6e64d68e263", "type": "Gene", "text": [ "DUTT1" ], "offsets": [ [ 658, 663 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4f7e1be5-cdd2-4b5b-8f59-8fcd2281b450", "type": "Gene", "text": [ "ROBO2" ], "offsets": [ [ 665, 670 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "562ac4ee-7523-4f20-9b01-79a6b6fbd04a", "type": "Gene", "text": [ "ROBO1" ], "offsets": [ [ 758, 763 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ea5a7ae1-b5a6-46fb-929a-305f95e30aa9", "type": "Gene", "text": [ "DUTT1" ], "offsets": [ [ 764, 769 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "25e52b6a-11f6-4d93-8121-da17a429910d", "type": "Gene", "text": [ "ROBO2" ], "offsets": [ [ 774, 779 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "93b14030-8a82-4816-93ee-41a11af85ac7", "type": "Gene", "text": [ "ROBO1" ], "offsets": [ [ 960, 965 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4adda166-110a-474c-bdc6-e1110f7b5c94", "type": "Gene", "text": [ "DUTT1" ], "offsets": [ [ 966, 971 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d04220da-18fa-4c98-8c55-b5e3b6119713", "type": "Gene", "text": [ "ROBO2" ], "offsets": [ [ 977, 982 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d0cd79f8-7788-49d9-b669-4eff038646dc", "type": "Gene", "text": [ "ROBO1" ], "offsets": [ [ 1267, 1272 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "dca8720c-4748-4463-9b8e-a4d986034d96", "type": "Gene", "text": [ "DUTT1" ], "offsets": [ [ 1273, 1278 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "34f0afaa-3e4c-4ec7-a7b2-6593d09b0c3f", "type": "Gene", "text": [ "ROBO2" ], "offsets": [ [ 1283, 1288 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3d6cddc5-470a-4ffb-9805-767c611a3b8e", "type": "Gene", "text": [ "ROBO1" ], "offsets": [ [ 1376, 1381 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "726156ab-a395-4a74-8596-9f87b7764315", "type": "Gene", "text": [ "DUTT1" ], "offsets": [ [ 1382, 1387 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c1944da3-f0b8-4cb9-8880-9eaec68ddb59", "type": "Gene", "text": [ "ROBO2" ], "offsets": [ [ 1392, 1397 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b3ab4136-6a9e-48ce-a6d2-6ecf5f1c6cf1", "type": "Gene", "text": [ "ROBO1" ], "offsets": [ [ 1545, 1550 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2a943bde-51f7-4525-9c6a-6a68158f55eb", "type": "Gene", "text": [ "DUTT1" ], "offsets": [ [ 1551, 1556 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "09a1c0b7-ce66-43cc-8641-0d995ba1d02a", "type": "Gene", "text": [ "nodal" ], "offsets": [ [ 1590, 1595 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "dd1c4561-f440-4492-a3d3-46a3afd650cc", "type": "Gene", "text": [ "ROBO1" ], "offsets": [ [ 1631, 1636 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8c05e4e3-3a7e-4b53-9aa4-017f38a3735e", "type": "Gene", "text": [ "DUTT1" ], "offsets": [ [ 1637, 1642 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ff6558d5-f8d7-48c1-b3f3-cab3a979f6be", "type": "Gene", "text": [ "ROBO1" ], "offsets": [ [ 1724, 1729 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "14e8ce39-cdc2-497f-a897-17c7b474fa2f", "type": "Gene", "text": [ "DUTT1" ], "offsets": [ [ 1730, 1735 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "6d89587e-3c26-495b-8ffe-6e0e78c0c0a5", "type": "title", "text": [ "Familial occurrence of schwannomas and malignant rhabdoid tumour associated with a duplication in SMARCB1." ], "offsets": [ [ 0, 106 ] ] }, { "id": "bae117b9-34dc-4a67-8b14-4f46fd12e3b7", "type": "abstract", "text": [ "BACKGROUND: The role of germline and somatic SMARCB1 gene mutations in malignant rhabdoid tumour (MRT) predisposition is well known. Germline SMARCB1 mutations have also recently been identified in a subset of individuals with schwannomatosis. Surprisingly, MRT predisposition and schwannomatosis have never been reported to co-occur in a family. The correlation between genotype and phenotype for mutations in SMARCB1 has not been determined. RESULTS: We have identified a germline 2631 bp duplication that includes exon 6 of SMARCB1 in a unique family with a four generation history of MRT predisposition and schwannomatosis. This duplication segregates with disease in individuals affected with both conditions, linking MRT predisposition and schwannomatosis as components of the same syndrome in this family. CONCLUSION: The unique combination of tumours that result from the duplication described in this report may provide important clues about the mechanisms that influence the phenotype associated with a given SMARCB1 mutation." ], "offsets": [ [ 107, 1143 ] ] } ]

[ { "id": "f6c7d9b6-bdb7-4aaa-b2bd-77b749ab6c73", "type": "Gene", "text": [ "SMARCB1" ], "offsets": [ [ 98, 105 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ad01aa3c-440c-4d61-b76a-2aeb5b5d15e7", "type": "Gene", "text": [ "SMARCB1" ], "offsets": [ [ 152, 159 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "de023ce1-1664-48b7-b9f3-df2fb6c19072", "type": "Gene", "text": [ "SMARCB1" ], "offsets": [ [ 249, 256 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d66a861a-314a-4064-bc5f-54df8f2f8a9d", "type": "Gene", "text": [ "SMARCB1" ], "offsets": [ [ 518, 525 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f2e07ff5-9120-48fe-9ec7-d83562a0f4bc", "type": "Gene", "text": [ "SMARCB1" ], "offsets": [ [ 634, 641 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1275b6a2-dc15-40af-91d6-2acf44fe75a4", "type": "Gene", "text": [ "SMARCB1" ], "offsets": [ [ 1126, 1133 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "688ee36f-be7b-4df4-8a17-dce62079398e", "type": "title", "text": [ "P2RX7: A bipolar and unipolar disorder candidate susceptibility gene?" ], "offsets": [ [ 0, 69 ] ] }, { "id": "c8156b14-2489-499e-a0a7-7f8a93410907", "type": "abstract", "text": [ "The chromosomal region 12q24 has been previously implicated by linkage studies of both bipolar disorder and unipolar mood disorder and we have reported two pedigrees segregating both bipolar disorder and Darier's disease that show linkage across this region. The gene P2RX7 is located in this chromosomal region and has been recently reported as a susceptibility gene for bipolar disorder and unipolar depression. The non-synonymous SNP rs2230912 (resulting in amino-acid polymorphism Q460R) showed the strongest association and has been postulated to be pathogenically relevant. We have investigated this gene in a large UK case-control sample (bipolar I disorder N = 687, unipolar recurrent major depression N = 1,036, controls N = 1,204). Neither rs2230912 nor any of 8 other SNPs genotyped across P2RX7 was found to be associated with mood disorder in general, nor specifically with bipolar or unipolar disorder. Further, sequencing of our two chromosome 12-linked bipolar-Darier families showed no evidence of rare variants at P2RX7 that could explain the linkage. Our data do not provide support for rs2230912 or the other polymorphisms studied within the P2RX7 locus, being involved in susceptibility to mood disorders." ], "offsets": [ [ 70, 1301 ] ] } ]

[ { "id": "c9e45842-5b83-4548-9068-3b79545d38b8", "type": "Gene", "text": [ "P2RX7" ], "offsets": [ [ 0, 5 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9b619a68-b5c4-4544-800e-7d104a196152", "type": "FamilyName", "text": [ "unipolar disorder candidate susceptibility gene" ], "offsets": [ [ 21, 68 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e2795c32-2615-4e52-8c49-ddd9053a9b25", "type": "Gene", "text": [ "P2RX7" ], "offsets": [ [ 343, 348 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "dca16b33-b2db-442b-9f43-89170d87bf56", "type": "Gene", "text": [ "P2RX7" ], "offsets": [ [ 876, 881 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7bd427dd-2f62-4932-99c1-6d6a24181a6c", "type": "Gene", "text": [ "P2RX7" ], "offsets": [ [ 1107, 1112 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5d6794d3-57bc-47fd-ba02-4e77aef34b8f", "type": "Gene", "text": [ "P2RX7" ], "offsets": [ [ 1237, 1242 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "b4141bd6-7962-4030-bc1d-3b349baedf00", "type": "title", "text": [ "Growth hormone dose in growth hormone-deficient adults is not associated with IGF-1 gene polymorphisms." ], "offsets": [ [ 0, 103 ] ] }, { "id": "e5236eb8-9746-4f47-96ad-f21bf2057980", "type": "abstract", "text": [ "AIMS: Several SNPs and a microsatellite cytosine-adenine repeat promoter polymorphism of the IGF-1 gene have been reported to be associated with circulating IGF-1 serum concentrations. Variance in IGF-1 concentrations due to genetic variations may affect different response to growth hormone (GH) treatment, resulting in different individually required GH-doses in GH-deficient patients. The aim of this study was to test if the IGF-1 gene polymorphisms are associated with the GH-dose of GH-deficient adults. MATERIALS & METHODS: A total of nine tagging SNPs, five additionally selected SNPs and a cytosine-adenine repeat polymorphism were determined in 133 German adult patients (66 men, 67 women; mean age 45.4 years +/- 13.1 standard deviation; majority Caucasian) with GH-deficiency (GHD) of different origin, derived from the prospective Pfizer International Metabolic Study (KIMS) Pharmacogenetics Study. Patients received GH-treatment for 12 months with finished dose-titration of GH and centralized IGF-1 measurements. GH-dose after 1 year of treatment, IGF-1 concentrations, IGF-1-standard deviation score (SDS), the IGF-1:GH ratio and anthropometric data were analyzed by genotype. RESULTS: Except for rs1019731, which showed a significant difference of IGF-1-SDS by genotypes (p = 0.02), all polymorphisms showed no associations with the GH-doses, IGF-1 concentrations, IGF-1-SDS and IGF-1:GH ratio after adjusting for the confounding variables gender, age and BMI. CONCLUSION: IGF-1 gene polymorphisms were not associated with the responsiveness to exogenous GH in GHD. Therefore, genetic variations of the IGF-1 gene seem not to be major influencing factors of the GH-IGF-axis causing variable response to exogenous GH-treatment." ], "offsets": [ [ 104, 1851 ] ] } ]

[ { "id": "00a39ce8-21d7-4af2-8877-48b171488b55", "type": "Gene", "text": [ "Growth hormone" ], "offsets": [ [ 0, 14 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "96330223-9e30-41d1-aca8-6db6c5865c05", "type": "Gene", "text": [ "growth hormone" ], "offsets": [ [ 23, 37 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a27d361d-eeff-4dbb-bf11-02210b22c4f4", "type": "Gene", "text": [ "IGF-1" ], "offsets": [ [ 78, 83 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "56f0c0ae-a5e1-4921-830a-259581072083", "type": "Gene", "text": [ "IGF-1" ], "offsets": [ [ 197, 202 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e5f5ebe5-9bfa-4016-af70-fb36fc030c5d", "type": "Gene", "text": [ "IGF-1" ], "offsets": [ [ 261, 266 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d8fee156-0e60-4835-9527-6c4900f3f2e8", "type": "Gene", "text": [ "IGF-1" ], "offsets": [ [ 301, 306 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d7127086-e5d1-4cd1-a677-0b7fbb8fd5a3", "type": "Gene", "text": [ "growth hormone" ], "offsets": [ [ 381, 395 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "bdcab36f-7be7-4b86-ae9f-b02a85f6ddac", "type": "Gene", "text": [ "GH" ], "offsets": [ [ 397, 399 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7063aaa5-7e90-4c91-9bea-a1384f83cd21", "type": "Gene", "text": [ "GH" ], "offsets": [ [ 457, 459 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8d7703a8-acbd-4e3f-bcc0-71cd02a75fcc", "type": "Gene", "text": [ "GH" ], "offsets": [ [ 469, 471 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "125994c7-1b28-48c8-a668-6bc959a57032", "type": "Gene", "text": [ "IGF-1" ], "offsets": [ [ 533, 538 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "97e70411-791f-4f05-81ba-370299d3fbcd", "type": "Gene", "text": [ "GH" ], "offsets": [ [ 582, 584 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "111b62f3-5e08-4105-89bc-7005770c08b9", "type": "Gene", "text": [ "GH" ], "offsets": [ [ 593, 595 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6a9a364c-ca8e-47a8-bac4-940c428c7f80", "type": "Gene", "text": [ "GH" ], "offsets": [ [ 882, 884 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "29e3e58a-a385-4214-9c33-a52cb185dac8", "type": "Gene", "text": [ "GH" ], "offsets": [ [ 1038, 1040 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5b6264bb-aea1-4d45-b888-8960dc371119", "type": "Gene", "text": [ "GH" ], "offsets": [ [ 1097, 1099 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e872f426-f41e-4a83-b32f-a416b8d1c041", "type": "Gene", "text": [ "IGF-1" ], "offsets": [ [ 1116, 1121 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ac852067-de9b-416c-8421-f06709fe010a", "type": "Gene", "text": [ "GH" ], "offsets": [ [ 1136, 1138 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "05ec7149-f2fa-4d8d-98b6-7ca9c53e7fda", "type": "Gene", "text": [ "IGF-1" ], "offsets": [ [ 1171, 1176 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0c349d5f-8a0b-477d-9812-66b846c94521", "type": "Gene", "text": [ "IGF-1" ], "offsets": [ [ 1193, 1198 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9041adfc-30ea-417f-9a82-ad128c23921e", "type": "Gene", "text": [ "IGF-1" ], "offsets": [ [ 1235, 1240 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9dc6f63b-61be-47d5-bac0-9697be8e705d", "type": "Gene", "text": [ "GH" ], "offsets": [ [ 1241, 1243 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b773ebdb-42cc-4540-8029-e69200666f07", "type": "Gene", "text": [ "IGF-1" ], "offsets": [ [ 1373, 1378 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "423ce18c-7d23-4281-8a7b-c8ba04771b67", "type": "Gene", "text": [ "GH" ], "offsets": [ [ 1458, 1460 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "eb970f8e-68f1-462a-a9e6-49fdf29ff911", "type": "Gene", "text": [ "IGF-1" ], "offsets": [ [ 1468, 1473 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e265014e-4a44-4327-b6de-a57671899fad", "type": "Gene", "text": [ "IGF-1" ], "offsets": [ [ 1490, 1495 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "423769b8-a46d-4f69-9a04-1f9af99e8ee6", "type": "Gene", "text": [ "IGF-1" ], "offsets": [ [ 1504, 1509 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e5756674-e062-4117-ac69-f9f4d9e62739", "type": "Gene", "text": [ "GH" ], "offsets": [ [ 1510, 1512 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "068f186a-fb40-46f0-b978-04e5d02a290d", "type": "Gene", "text": [ "IGF-1" ], "offsets": [ [ 1598, 1603 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ced212a3-bf7d-4c26-8364-4cbe3ab5f365", "type": "Gene", "text": [ "GH" ], "offsets": [ [ 1680, 1682 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8fa338e2-b826-4f5a-95cc-25729ed25289", "type": "Gene", "text": [ "IGF-1" ], "offsets": [ [ 1728, 1733 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d6a9f562-7fba-42bd-921c-6848da8bd704", "type": "Gene", "text": [ "GH" ], "offsets": [ [ 1787, 1789 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "402b87b2-a06f-4ede-982a-607f886ff651", "type": "Gene", "text": [ "GH" ], "offsets": [ [ 1838, 1840 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "b2967f6d-4874-49ad-a205-fb08a6c1a9b3", "type": "title", "text": [ "Osteogenesis imperfecta type III with intracranial hemorrhage and brachydactyly associated with mutations in exon 49 of COL1A2." ], "offsets": [ [ 0, 127 ] ] }, { "id": "e8bcf1b2-4362-4fd2-942f-1232006cba23", "type": "abstract", "text": [ "Osteogenesis imperfecta (OI) is a heritable bone disorder characterized by fractures with minimal trauma. Intracranial hemorrhage has been reported in a small number of OI patients. Here we describe three patients, a boy (aged 15 years) and two girls (aged 17 and 7 years) with OI type III who suffered intracranial hemorrhage and in addition had brachydactyly and nail hypoplasia. In all of these patients, OI was caused by glycine mutations affecting exon 49 of the COL1A2 gene, which codes for the most carboxy-terminal part of the triple-helical domain of the collagen type I alpha 2 chain. These observations suggest that mutations in this region of the collagen type I alpha 2 chain carry a high risk of abnormal limb development and intracranial bleeding." ], "offsets": [ [ 128, 890 ] ] } ]

[ { "id": "5f6a2339-9b7c-4a15-a8ff-14560df920e7", "type": "Gene", "text": [ "COL1A2" ], "offsets": [ [ 120, 126 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6fd74d1a-54c4-4a4e-b056-95c9f257a5c2", "type": "Gene", "text": [ "COL1A2" ], "offsets": [ [ 596, 602 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4c35a4cb-0379-40b3-b7be-b34aff90df57", "type": "DomainMotif", "text": [ "triple-helical domain" ], "offsets": [ [ 663, 684 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "037f7003-c59d-4715-9b25-7e7dc76c37ca", "type": "Gene", "text": [ "collagen type I alpha 2" ], "offsets": [ [ 692, 715 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3076cd7e-83d0-470c-93f6-e27009531f98", "type": "Gene", "text": [ "collagen type I alpha 2" ], "offsets": [ [ 787, 810 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "a09a583e-7435-43cd-8511-6388c6d98353", "type": "title", "text": [ "Quantitative PCR high-resolution melting (qPCR-HRM) curve analysis, a new approach to simultaneously screen point mutations and large rearrangements: application to MLH1 germline mutations in Lynch syndrome." ], "offsets": [ [ 0, 207 ] ] }, { "id": "792251a2-4d51-40ea-a645-e8b838451ba9", "type": "abstract", "text": [ "Several techniques have been developed to screen mismatch repair (MMR) genes for deleterious mutations. Until now, two different techniques were required to screen for both point mutations and large rearrangements. For the first time, we propose a new approach, called "quantitative PCR (qPCR) high-resolution melting (HRM) curve analysis (qPCR-HRM)," which combines qPCR and HRM to obtain a rapid and cost-effective method suitable for testing a large series of samples. We designed PCR amplicons to scan the MLH1 gene using qPCR HRM. Seventy-six patients were fully scanned in replicate, including 14 wild-type patients and 62 patients with known mutations (57 point mutations and five rearrangements). To validate the detected mutations, we used sequencing and/or hybridization on a dedicated MLH1 array-comparative genomic hybridization (array-CGH). All point mutations and rearrangements detected by denaturing high-performance liquid chromatography (dHPLC)+multiplex ligation-dependent probe amplification (MLPA) were successfully detected by qPCR HRM. Three large rearrangements were characterized with the dedicated MLH1 array-CGH. One variant was detected with qPCR HRM in a wild-type patient and was located within the reverse primer. One variant was not detected with qPCR HRM or with dHPLC due to its proximity to a T-stretch. With qPCR HRM, prescreening for point mutations and large rearrangements are performed in one tube and in one step with a single machine, without the need for any automated sequencer in the prescreening process. In replicate, its reagent cost, sensitivity, and specificity are comparable to those of dHPLC+MLPA techniques. However, qPCR HRM outperformed the other techniques in terms of its rapidity and amount of data provided." ], "offsets": [ [ 208, 1985 ] ] } ]

[ { "id": "28c67c6e-d119-42ac-bb4d-24548ffda39b", "type": "Gene", "text": [ "MLH1" ], "offsets": [ [ 165, 169 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "19eb17f6-871a-4c42-ad5f-3aad23bb4fb7", "type": "FamilyName", "text": [ "mismatch repair" ], "offsets": [ [ 257, 272 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "975d17bc-8591-4747-b9b1-3daaa90e7c89", "type": "FamilyName", "text": [ "MMR" ], "offsets": [ [ 274, 277 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c1ac433d-f68b-4b2a-aeff-47e237c4d260", "type": "Gene", "text": [ "MLH1" ], "offsets": [ [ 728, 732 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "69c31cbc-66f8-4966-97ac-2559cbb7d6d5", "type": "Gene", "text": [ "MLH1" ], "offsets": [ [ 1014, 1018 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "eca68133-2b1d-40b9-8bde-36314422e6bc", "type": "Gene", "text": [ "MLH1" ], "offsets": [ [ 1342, 1346 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "22a7c2d0-8bfa-426f-90c4-d0987adcf589", "type": "title", "text": [ "SCA-LSVD: a repeat-oriented locus-specific variation database for genotype to phenotype correlations in spinocerebellar ataxias." ], "offsets": [ [ 0, 128 ] ] }, { "id": "7b20eb71-b7f6-479f-ab06-f8d51faf7d6f", "type": "abstract", "text": [ "Repeat expansion has been implicated in 10 out of 17 candidate genes identified for autosomal dominant cerebellar ataxias (ADCAs)-commonly referred as spinocerebellar ataxias (SCAs). Though genetically distinct, the SCAs share a large number of features that confound their clinical classification. In addition, there is a difference in the prevalence and phenotypic expression of ataxias between different ethnic groups. We have created a new SCA-locus-specific variation database (LSVD) that aims to catalog and integrate information on SCAs associated with trinucleotide repeat expansion (SCA1, SCA 2, SCA 3, SCA 6, SCA 7, SCA 8, SCA 12, SCA 17, Friedreich's ataxia [FRDA], and dentatorubral-pallidoluysian atrophy [DRPLA]) from all over the world. The database has been developed using the Leiden Open (source) Variation Database (LOVD) software (Leiden University Medical Center, Leiden, the Netherlands). The database houses detailed information on clinical features, such as age and symptom at onset, mode of inheritance, and genotype information, pertaining to the SCA patients from more than 400 families across India. All the compiled genotype data conforms to the HGVS Nomenclature guidelines. This would be a very useful starting point for understanding the molecular correlates of phenotypes in ataxia-a multilocus disease in which related molecular mechanisms converge to overlapping phenotypes." ], "offsets": [ [ 129, 1543 ] ] } ]

[ { "id": "5e04f906-e0ac-4a1c-ade7-9c0625bff8ca", "type": "Gene", "text": [ "SCA1" ], "offsets": [ [ 721, 725 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fc8808c7-437d-4da0-b35b-e1282ffe6928", "type": "Gene", "text": [ "SCA 2" ], "offsets": [ [ 727, 732 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "902588cf-2132-4c95-be2f-9367c32db37e", "type": "Gene", "text": [ "SCA 3" ], "offsets": [ [ 734, 739 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a798fcb7-0aeb-4432-b9ea-dfa022321ab3", "type": "Gene", "text": [ "SCA 6" ], "offsets": [ [ 741, 746 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "62883006-5699-4d70-91ec-b13a5f98b5a0", "type": "Gene", "text": [ "SCA 7" ], "offsets": [ [ 748, 753 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fc6c0b2e-c2f5-4d50-ae37-931f5ce39343", "type": "Gene", "text": [ "SCA 8" ], "offsets": [ [ 755, 760 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cb881cf3-97f2-42e8-8b6a-adf9021019f1", "type": "Gene", "text": [ "SCA 12" ], "offsets": [ [ 762, 768 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c74c768d-6840-4ebd-b0a1-22213c401679", "type": "Gene", "text": [ "SCA 17" ], "offsets": [ [ 770, 776 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "06669687-d51f-4146-a3af-215241190988", "type": "title", "text": [ "Systematic screening for polymorphisms within the UGT1A6 gene in three Chinese populations and function prediction through structural modeling." ], "offsets": [ [ 0, 143 ] ] }, { "id": "e7454a1e-1681-4364-a8d4-92d06fce8c3a", "type": "abstract", "text": [ "AIMS: To date, there have been relatively few studies on the UGT1A6 gene in the Chinese population. The present study was designed to determine the allele frequencies and haplotypes of this gene in the population and predict the candidate functional mutations. MATERIALS & METHODS: We carried out the first systematic screening of polymorphisms of the gene in an SNP analysis involving 1074 Chinese subjects from three ethnic groups, namely Han, Dong and She, using direct sequencing. We identified the putative substrate binding pocket using a homology-modeled structure and produced a practical model for predicting the function of polymorphisms in UGT1A6. RESULTS: A total of six SNPs and 10 mutations were detected including nine known and seven novel ones. The novel mutations were 73G>A (V25I), 89T>G (L30R), 222A>C, 657C>A, 773A>T (D258V), 1040A>G (N347S) and 1467C>T. In addition, we detected, for the first time in the Chinese population, SNPs 105C>T, 627G>T as well as mutations 308C>A (S103X), IVS2+15T>C and 1088C>T (P363L). Strong linkage disequilibrium was observed among 19T>G, 315A>G, 541A>G and 552A>C. There were seven haplotypes whose frequencies were more than 0.01 in one or more of the three ethnic groups. P363L in the C-terminal domain might weaken the binding of cofactor UDPGA to the domain and induce a poor metabolism genotype of UGT1A6. CONCLUSION: Our study suggests that genetic polymorphisms in UGT1A6 may contribute to interindividual and intra-ethnic differences. The results should prove helpful in the development of pharmacogenomics in China." ], "offsets": [ [ 144, 1775 ] ] } ]

[ { "id": "76a247f7-15fc-465e-82a3-1ec77181e942", "type": "Gene", "text": [ "UGT1A6" ], "offsets": [ [ 50, 56 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b23c4406-84d4-45d8-931c-d8afe09026a6", "type": "Gene", "text": [ "UGT1A6" ], "offsets": [ [ 205, 211 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e044ba5a-d1f4-491c-a0d3-048389421695", "type": "Gene", "text": [ "UGT1A6" ], "offsets": [ [ 799, 805 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "efd44a62-a819-4ff4-8652-809e155d2d7f", "type": "DomainMotif", "text": [ "C-terminal domain" ], "offsets": [ [ 1438, 1455 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9768927e-3bdd-4ecf-96ff-f768ffa578fc", "type": "Gene", "text": [ "UGT1A6" ], "offsets": [ [ 1554, 1560 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c2470ca9-d56f-4d4e-a3bd-e7fa01771fcd", "type": "Gene", "text": [ "UGT1A6" ], "offsets": [ [ 1623, 1629 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "3bef0507-c3a8-4526-8310-8ee3b408cc3f", "type": "title", "text": [ "Vascular endothelial growth factor gene polymorphisms as prognostic markers for ocular manifestations in pseudoxanthoma elasticum." ], "offsets": [ [ 0, 130 ] ] }, { "id": "30591bed-2700-4ef4-a7ea-8a6743fcaa27", "type": "abstract", "text": [ "Pseudoxanthoma elasticum (PXE) is a heritable disorder affecting the skin, eyes and cardiovascular system. It is caused by mutations in the ABCC6 gene and its clinical picture is highly variable. PXE often leads to severe visual impairment due to the development of choroidal neovascularisation (CNV). CNV in PXE-associated retinopathy is believed to be mediated by the action of vascular endothelial growth factor (VEGF). The objective of the present study was to evaluate a possible impact of variations in the VEGFA gene on ocular manifestations of PXE. For this purpose, we evaluated the distribution of 10 single nucleotide polymorphisms (SNPs) in the promoter and coding region of the VEGFA gene in DNA samples from 163 German patients affected by PXE and in 163 healthy control subjects. Haplotype analysis of SNPs c.-1540A>C, c.-460C>T, c.-152G>A, c.405C>G, c.674C>T, c.1032C>T, c.4618C>T and c.5092C>A revealed that the haplotype CTGGCCCC was associated with PXE (OR 2.05, 95% CI 1.33-3.15, P(corrected) = 0.01). Furthermore, five SNPs showed significant association with severe retinopathy. The most significant single SNP association was c.-460C>T (OR 3.83, 95% CI 2.01-7.31, P(corrected) = 0.0003). Logistic regression analysis identified the c.-460T and the c.674C alleles as independent risk factors for development of severe retinopathy. Our findings suggest an involvement of VEGF in the pathogenesis of ocular PXE manifestations. VEGF gene polymorphisms might prove useful as prognostic markers for the development of PXE-associated retinopathy and permit earlier therapeutic intervention in order to prevent loss of central vision, one of the most devastating consequences of this disease." ], "offsets": [ [ 131, 1865 ] ] } ]

[ { "id": "5914aea4-773c-4f97-a41f-8014c1fcb33b", "type": "Gene", "text": [ "Vascular endothelial growth factor" ], "offsets": [ [ 0, 34 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3e6b9dd2-a919-453e-9a1f-96a69a8892a4", "type": "Gene", "text": [ "ABCC6" ], "offsets": [ [ 271, 276 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "514edc00-9634-4b46-909f-07a83cab8783", "type": "Gene", "text": [ "vascular endothelial growth factor" ], "offsets": [ [ 511, 545 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "43cac161-f94c-42b5-9681-5d21331e182c", "type": "Gene", "text": [ "VEGF" ], "offsets": [ [ 547, 551 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "edfefb1a-774c-4b25-b8cf-6d159950efa7", "type": "Gene", "text": [ "VEGFA" ], "offsets": [ [ 644, 649 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cd5b9d26-1cad-44a9-a720-b8fa7b6a4b4c", "type": "Gene", "text": [ "VEGFA" ], "offsets": [ [ 822, 827 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "07ff7777-173c-42f7-8cc8-369f1a368b4c", "type": "Gene", "text": [ "VEGF" ], "offsets": [ [ 1550, 1554 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ab61937a-aeeb-446a-aa19-7906a0c3231c", "type": "Gene", "text": [ "VEGF" ], "offsets": [ [ 1605, 1609 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "a1af89b1-8e5e-4df3-9b01-174af181c1cd", "type": "title", "text": [ "Hypomorphic mutations in meckelin (MKS3/TMEM67) cause nephronophthisis with liver fibrosis (NPHP11)." ], "offsets": [ [ 0, 100 ] ] }, { "id": "b5d723e1-4767-4330-9352-a31617dc9429", "type": "abstract", "text": [ "BACKGROUND: Nephronophthisis (NPHP), a rare recessive cystic kidney disease, is the most frequent genetic cause of chronic renal failure in children and young adults. Mutations in nine genes (NPHP1-9) have been identified. NPHP can be associated with retinal degeneration (Senior-Loken syndrome), brainstem and cerebellar anomalies (Joubert syndrome), or liver fibrosis. METHODS: To identify a causative gene for the subset of patients with associated liver fibrosis, the authors performed a genome wide linkage search in a consanguineous family with three affected patients using 50K SNP microarrays and homozygosity mapping. RESULTS: The authors obtained a significant maximum parametric LOD (logarithm of odds) score of Z(max) = 3.72 on chromosome 8q22 and identified a homozygous missense mutation in the gene MKS3/TMEM67. When examining a worldwide cohort of 62 independent patients with NPHP and associated liver fibrosis we identified altogether four novel mutations (p.W290L, p.C615R, p.G821S, and p.G821R) in five of them. Mutations of MKS3/TMEM67, found recently in Meckel-Gruber syndrome (MKS) type 3 and Joubert syndrome (JBTS) type 6, are predominantly truncating mutations. In contrast, the mutations detected here in patients with NPHP and associated liver fibrosis are exclusively missense mutations. This suggests that they may represent hypomorphic alleles, leading to a milder phenotype compared with the more severe MKS or JBTS phenotype. Additionally, mutation analysis for MKS3/TMEM67 in 120 patients with JBTS yielded seven different (four novel) mutations in five patients, four of whom also presented with congenital liver fibrosis. CONCLUSIONS: Hypomorphic MKS3/TMEM67 mutations cause NPHP with liver fibrosis (NPHP11). This is the first report of MKS3 mutations in patients with no vermian agenesis and without neurological signs. Thus NPHP, JBTS, and MKS represent allelic disorders." ], "offsets": [ [ 101, 2012 ] ] } ]

[ { "id": "43230dc7-d378-4df1-a31f-854c11a38bbe", "type": "Gene", "text": [ "meckelin" ], "offsets": [ [ 25, 33 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "649b7093-adad-4090-8e64-119a98872ca0", "type": "Gene", "text": [ "MKS3" ], "offsets": [ [ 35, 39 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a41d2b56-0d13-4a91-8f26-07013d2d01de", "type": "Gene", "text": [ "TMEM67" ], "offsets": [ [ 40, 46 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b73b6fe4-3afc-40c5-9186-260c873bd3ab", "type": "Gene", "text": [ "NPHP11" ], "offsets": [ [ 92, 98 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c95be359-8423-4af5-9ccc-a0e445670b40", "type": "Gene", "text": [ "NPHP1-9" ], "offsets": [ [ 293, 300 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4f2793ae-6399-4beb-86f1-280dd2c58797", "type": "Gene", "text": [ "MKS3" ], "offsets": [ [ 915, 919 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b859bcb6-a373-4fd4-b1a1-ec154d06510f", "type": "Gene", "text": [ "TMEM67" ], "offsets": [ [ 920, 926 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "393ad890-e3e8-477b-8124-bb15d70e5971", "type": "Gene", "text": [ "MKS3" ], "offsets": [ [ 1146, 1150 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e6f795dd-c5b0-4508-925a-58a268f3dfd4", "type": "Gene", "text": [ "TMEM67" ], "offsets": [ [ 1151, 1157 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c5486468-ff1f-451e-872a-773aa22dd520", "type": "Gene", "text": [ "MKS3" ], "offsets": [ [ 1596, 1600 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2ae3c29d-6e1a-46f8-92b9-1bdc43b1ee50", "type": "Gene", "text": [ "TMEM67" ], "offsets": [ [ 1601, 1607 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e67899ee-b391-4b91-ad72-0be76c88738a", "type": "Gene", "text": [ "MKS3" ], "offsets": [ [ 1784, 1788 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e73efe6c-7051-45e2-a9fd-675a691be340", "type": "Gene", "text": [ "TMEM67" ], "offsets": [ [ 1789, 1795 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "893d315c-3c95-414c-b931-7fc0fd28ed32", "type": "Gene", "text": [ "NPHP11" ], "offsets": [ [ 1838, 1844 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ea54ecdb-7e39-4b78-a897-ed07061dbb16", "type": "Gene", "text": [ "MKS3" ], "offsets": [ [ 1875, 1879 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "24e70ec5-8cbe-428c-a057-b25250895a07", "type": "title", "text": [ "The role of the COMT Val(158)Met polymorphism in the phenotypic expression of obsessive-compulsive disorder." ], "offsets": [ [ 0, 108 ] ] }, { "id": "8bbafe8a-8117-4333-94e8-9d37e04e39bd", "type": "abstract", "text": [ "Obsessive-Compulsive Disorder (OCD) is characterized by the presence of obsessions and compulsions, and shows considerable phenotypic variability. Family and twin studies have indicated a genetic component in the etiology of OCD, and the catechol-O-methyl transferase (COMT) gene is an important candidate gene for OCD. This study investigates the influence of the functional COMT Val158Met polymorphism on the phenotypic expression of OCD, using an item-level factor-analytic approach in a large sample. The COMT Val158Met variant was genotyped in 373 patients and 462 controls. It was tested whether there was an association between the COMT Val158Met polymorphism and OCD or dimensional phenotypes such as YBOCS severity score, age of onset of obsessive-compulsive symptoms and six symptom dimensions recently found in a large item-level factor-analytic study [Katerberg et al., submitted]. We further investigated possible sex-specific associations between the COMT Val158Met polymorphism and OCD or dimensional phenotypes. There was a trend for an association of the COMT 158Met allele with OCD in males, and an interaction between the COMT Val158Met genotype and sex on the somatic and sensory phenomena symptom dimension, with females showing lower scores. In conclusion, a dimensional approach seems fruitful in detecting genes of importance for OCD." ], "offsets": [ [ 109, 1467 ] ] } ]

[ { "id": "b68cf8eb-436b-4b84-8427-591cb12c0744", "type": "Gene", "text": [ "COMT" ], "offsets": [ [ 16, 20 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "edcaaeed-bb46-45a6-ada1-abcbbe326cae", "type": "Gene", "text": [ "catechol-O-methyl transferase" ], "offsets": [ [ 347, 376 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0615e1cb-38ff-4ddb-b639-2e1cd49463cc", "type": "Gene", "text": [ "COMT" ], "offsets": [ [ 378, 382 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1c18ced8-25e3-487f-a390-41e5745221a9", "type": "Gene", "text": [ "COMT" ], "offsets": [ [ 485, 489 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c94ad532-f722-45d5-81f4-22c1619ba565", "type": "Gene", "text": [ "COMT" ], "offsets": [ [ 618, 622 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "208823b9-6392-4480-9e93-3906dc74d0d5", "type": "Gene", "text": [ "COMT" ], "offsets": [ [ 748, 752 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5a3dccd3-68f8-4cfe-9cf7-58cf7189aa8c", "type": "Gene", "text": [ "COMT" ], "offsets": [ [ 1074, 1078 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a4a20379-71f7-4471-999a-56a08e93ac02", "type": "Gene", "text": [ "COMT" ], "offsets": [ [ 1181, 1185 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4b4afdca-7cc0-4f03-988f-fc4278995ca3", "type": "Gene", "text": [ "COMT" ], "offsets": [ [ 1250, 1254 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "822881aa-4563-48c6-ab2f-51ec065f02a8", "type": "title", "text": [ "UVB radiation induces human lens epithelial cell migration via NADPH oxidase-mediated generation of reactive oxygen species and up-regulation of matrix metalloproteinases." ], "offsets": [ [ 0, 171 ] ] }, { "id": "c84187f1-097d-4c51-9be5-3987475105b4", "type": "abstract", "text": [ "Ultraviolet (UV) radiation is one of the important cataract risk factors. The migration of human lens epithelial cells (HLECs) plays a crucial role in the remodeling of lens capsule and cataract formation. The purpose of the present study was to investigate the molecular mechanisms of UV-induced lens cell migration. We found that UVB radiation induces cell migration in cultured human lens epithelial cells. Further, we observed that UVB radiation induces NADPH oxidase activity and ROS generation which are inhibited by NADPH oxidase inhibitor diphenylene iodonium or DPI and antioxidant epigallocatechin gallate (EGCG). In addition, DPI and EGCG also block UVB irradiation-induced MMP-2, and -9 activity and expression and nuclear translocation of NF-kappaB. Collectively, our data suggest that NADPH oxidase may be a major source for the UVB-induced ROS generation, and it plays an essential role in the activation of NF-kappaB, which is involved in the activities of MMP-2 and MMP-9 and cell migration induced by UVB in HELCs. Understanding the cell signaling pathways may constitute potential therapeutic targets in for UVB-induced cataract." ], "offsets": [ [ 172, 1320 ] ] } ]

[ { "id": "caf0b6d4-d271-4104-b8b9-76ead698f00e", "type": "FamilyName", "text": [ "NADPH oxidase" ], "offsets": [ [ 63, 76 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a408c73c-4ccf-452a-bb05-4eb391c414c2", "type": "FamilyName", "text": [ "NADPH oxidase" ], "offsets": [ [ 630, 643 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c2e2bb7d-074a-4e1b-9eb5-962e24eecaaa", "type": "FamilyName", "text": [ "NADPH oxidase" ], "offsets": [ [ 695, 708 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "437010ef-64e0-4c52-a672-aaa846dfad1e", "type": "Gene", "text": [ "MMP-2, and -9" ], "offsets": [ [ 857, 870 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b61d39f8-6c10-4c11-a542-88fd7d6f977a", "type": "Gene", "text": [ "NF-kappaB" ], "offsets": [ [ 924, 933 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0665f1b1-2151-4863-805f-8e16bae5e7d9", "type": "FamilyName", "text": [ "NADPH oxidase" ], "offsets": [ [ 971, 984 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ca8b84ce-afe1-4f26-93cf-b2b048240d1d", "type": "Gene", "text": [ "NF-kappaB" ], "offsets": [ [ 1095, 1104 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ba486f95-5043-4f05-b8b0-a732c24963ba", "type": "Gene", "text": [ "MMP-2" ], "offsets": [ [ 1145, 1150 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c522d8e7-fba2-4a47-b7d8-6f2ccc57ca9c", "type": "Gene", "text": [ "MMP-9" ], "offsets": [ [ 1155, 1160 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "94a31d4f-770b-4b96-858f-11806658992e", "type": "title", "text": [ "A genome-wide in vitro bacterial-infection screen reveals human variation in the host response associated with inflammatory disease." ], "offsets": [ [ 0, 132 ] ] }, { "id": "2a531d4a-d364-45a9-816d-b2d96948f6b1", "type": "abstract", "text": [ "Recent progress in cataloguing common genetic variation has made possible genome-wide studies that are beginning to elucidate the causes and consequences of our genetic differences. Approaches that provide a mechanistic understanding of how genetic variants function to alter disease susceptibility and why they were substrates of natural selection would complement other approaches to human-genome analysis. Here we use a novel cell-based screen of bacterial infection to identify human variation in Salmonella-induced cell death. A loss-of-function allele of CARD8, a reported inhibitor of the proinflammatory protease caspase-1, was associated with increased cell death in vitro (p = 0.013). The validity of this association was demonstrated through overexpression of alternative alleles and RNA interference in cells of varying genotype. Comparison of mammalian CARD8 orthologs and examination of variation among different human populations suggest that the increase in infectious-disease burden associated with larger animal groups (i.e., herds and colonies), and possibly human population expansion, may have naturally selected for loss of CARD8. We also find that the loss-of-function CARD8 allele shows a modest association with an increased risk of systemic inflammatory response syndrome in a small study (p = 0.05). Therefore, a by-product of the selected benefit of loss of CARD8 could be increased inflammatory diseases. These results demonstrate the utility of genome-wide cell-based association screens with microbes in the identification of naturally selected variants that can impact human health." ], "offsets": [ [ 133, 1747 ] ] } ]

[ { "id": "f0d5c9c6-faef-43cd-bf32-bb16b5bff697", "type": "Gene", "text": [ "CARD8" ], "offsets": [ [ 694, 699 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0dc7f19c-c66a-4ae7-83f4-9975088aa182", "type": "FamilyName", "text": [ "proinflammatory protease" ], "offsets": [ [ 729, 753 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "62cd63f9-410e-4557-b229-9a2c8abfee98", "type": "Gene", "text": [ "caspase-1" ], "offsets": [ [ 754, 763 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1a1746dc-054a-4938-9cc6-dd3ff085c5a0", "type": "Gene", "text": [ "CARD8" ], "offsets": [ [ 999, 1004 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4acbc38d-e32b-4bad-9add-1e15f696930e", "type": "Gene", "text": [ "CARD8" ], "offsets": [ [ 1279, 1284 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a738c949-1192-4d09-a8ba-a9219c7baa09", "type": "Gene", "text": [ "CARD8" ], "offsets": [ [ 1325, 1330 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d8fc398f-6c65-49ad-be9e-e42dcb047361", "type": "Gene", "text": [ "CARD8" ], "offsets": [ [ 1519, 1524 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "a73ef868-0aca-4678-871f-888a9f53f6ed", "type": "title", "text": [ "Single nucleotide polymorphism in ABCG2 is associated with irinotecan-induced severe myelosuppression." ], "offsets": [ [ 0, 102 ] ] }, { "id": "444baf56-f940-409e-83a6-baab2b09e753", "type": "abstract", "text": [ "Irinotecan is an anti-neoplastic agent that is widely used for treating colorectal and lung cancers, but often causes toxicities such as severe myelosuppression and diarrhea. In this study, we performed a two-stage case-control association study for irinotecan-induced severe myelosuppression (grades 3 and 4). In the first stage, 23 patients who developed severe myelosuppression and 58 patients who did not develop any toxicity were examined for 170 single nucleotide polymorphisms (SNPs) in 14 genes involved in the metabolism and transport of irinotecan. A total of five SNPs were identified to show the possible association with severe myelosuppression (P(Fisher)<0.01) and were further examined in 7 cases and 20 controls in the second stage of the study. An intronic SNP, rs2622604, in ABCG2 showed P(Fisher)=0.0419 in the second stage and indicated a significant association with severe myelosuppression in the combined study (P(Fisher)=0.000237; P(Corrected)=0.036). Although only limited subjects were investigated, our results suggested that a genetic polymorphism in ABCG2 might alter the transport activity for the drug and elevate the systemic circulation level of irinotecan, leading to severe myelosuppression." ], "offsets": [ [ 103, 1332 ] ] } ]

[ { "id": "d8dfcb8c-2792-4746-969d-a782cdce078e", "type": "Gene", "text": [ "ABCG2" ], "offsets": [ [ 34, 39 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e5cc89c7-10e9-4bdc-bd0f-11749e9cb7f1", "type": "Gene", "text": [ "ABCG2" ], "offsets": [ [ 899, 904 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5aac2bb1-c259-4d74-ac3c-056610ec136c", "type": "Gene", "text": [ "ABCG2" ], "offsets": [ [ 1185, 1190 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "94f23d28-e4eb-45cc-a936-49b26e31007d", "type": "title", "text": [ "Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a South American family." ], "offsets": [ [ 0, 107 ] ] }, { "id": "5ae6d027-fef6-4381-9078-a8c791582016", "type": "abstract", "text": [ "Hypokalaemic periodic paralysis (HypoPP) is an autosomal dominant disorder, which is characterized by periodic attacks of muscle weakness associated with a decrease in the serum potassium level. A major disease-causing gene for HypoPP has been identified as CACNA1S, which encodes the skeletal muscle calcium channel alpha-subunit with four transmembrane domains (I-IV), each with six transmembrane segments (S1-S6). To date, all CACNA1S mutations identified in HypoPP patients are located within the voltage-sensor S4 segment. In this study we report a novel CACNA1S mutation in a new region of the protein, the S3 segment of domain III. We characterized a four-generation South American family with HypoPP. Genetic analysis identified a novel V876E mutation in all HypoPP patients in the family, but not in normal family members or 160 control people. Clinical analysis indicates that mutation V876E is associated with a severe outcome as characterized by a very early age of onset, complete penetrance and a severe prognosis including death. These results identify a new mutation in CACNA1S and expand the spectrum of CACNA1S mutations associated with HypoPP." ], "offsets": [ [ 108, 1270 ] ] } ]

[ { "id": "13d5ef40-1386-41da-8ee5-371dedef6ae2", "type": "Gene", "text": [ "CACNA1S" ], "offsets": [ [ 6, 13 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "dc217d07-5a24-4918-a7c6-b0d04bdd7891", "type": "Gene", "text": [ "CACNA1S" ], "offsets": [ [ 366, 373 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "87e130c4-5323-45d5-bcf3-52310f233e2f", "type": "DomainMotif", "text": [ "transmembrane domains" ], "offsets": [ [ 449, 470 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1f1c3cf7-88aa-498f-9279-2cd453e0b433", "type": "Gene", "text": [ "CACNA1S" ], "offsets": [ [ 538, 545 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2df9cd8c-5e24-4726-bd55-5982a748287b", "type": "Gene", "text": [ "CACNA1S" ], "offsets": [ [ 668, 675 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "57ea8074-a732-4f02-93ad-c61c4d8def50", "type": "Gene", "text": [ "CACNA1S" ], "offsets": [ [ 1194, 1201 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7cf6a39a-1419-41f8-905b-99506638566c", "type": "Gene", "text": [ "CACNA1S" ], "offsets": [ [ 1229, 1236 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "2fe19fe5-3e53-4107-9fca-950aa88cb5e6", "type": "title", "text": [ "Clopidogrel pharmacogenomics and risk of inadequate platelet inhibition: US FDA recommendations." ], "offsets": [ [ 0, 96 ] ] }, { "id": "f9774210-9cf7-41cb-af72-c7eb9b783ad4", "type": "abstract", "text": [ "Antiplatelet therapy with clopidogrel is the current standard of care for coronary artery disease patients undergoing a percutaneous coronary intervention. However, approximately 25% of patients experience a subtherapeutic antiplatelet response. Clopidogrel is a prodrug that undergoes hepatic biotransformation by CYP2C19 into its active metabolite. Several studies have reported that, compared with wild-type individuals, CYP2C19 variant allele carriers exhibit a significantly lower capacity to metabolize clopidogrel into its active metabolite and inhibit platelet activation, and are therefore at significantly higher risk of adverse cardiovascular events. Consequently, the US FDA has recently changed clopidogrel's prescribing information to highlight the impact of CYP2C19 genotype on clopidogrel pharmacokinetics, pharmacodynamics and clinical response. Future studies remain necessary to develop effective personalized therapeutic strategies for CYP2C19 variant allele carriers and other individuals at risk for clopidogrel nonresponsiveness." ], "offsets": [ [ 97, 1154 ] ] } ]

[ { "id": "0dc1fd45-b265-46be-8e9b-7efb8579647a", "type": "Gene", "text": [ "CYP2C19" ], "offsets": [ [ 412, 419 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a948666c-f9db-4037-8e9c-243aab23361e", "type": "Gene", "text": [ "CYP2C19" ], "offsets": [ [ 521, 528 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9709e896-4c44-44d6-a81b-5fa3f84cac94", "type": "Gene", "text": [ "CYP2C19" ], "offsets": [ [ 875, 882 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ebccc2a0-fae5-46b3-95c7-d413957d1517", "type": "Gene", "text": [ "CYP2C19" ], "offsets": [ [ 1058, 1065 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "cadaa4b9-7c58-4b4d-99a4-1468addb6e0f", "type": "title", "text": [ "DNA fragmentation in human fibroblasts under extremely low frequency electromagnetic field exposure." ], "offsets": [ [ 0, 100 ] ] }, { "id": "7308ba44-21b9-45fd-8cae-7a4875b8daf5", "type": "abstract", "text": [ "Extremely low frequency electromagnetic fields (ELF-EMFs) were reported to affect DNA integrity in human cells with evidence based on the Comet assay. These findings were heavily debated for two main reasons; the lack of reproducibility, and the absence of a plausible scientific rationale for how EMFs could damage DNA. Starting out from a replication of the relevant experiments, we performed this study to clarify the existence and explore origin and nature of ELF-EMF induced DNA effects. Our data confirm that intermittent (but not continuous) exposure of human primary fibroblasts to a 50 Hz EMF at a flux density of 1 mT induces a slight but significant increase of DNA fragmentation in the Comet assay, and we provide first evidence for this to be caused by the magnetic rather than the electric field. Moreover, we show that EMF-induced responses in the Comet assay are dependent on cell proliferation, suggesting that processes of DNA replication rather than the DNA itself may be affected. Consistently, the Comet effects correlated with a reduction of actively replicating cells and a concomitant increase of apoptotic cells in exposed cultures, whereas a combined Fpg-Comet test failed to produce evidence for a notable contribution of oxidative DNA base damage. Hence, ELF-EMF induced effects in the Comet assay are reproducible under specific conditions and can be explained by minor disturbances in S-phase processes and occasional triggering of apoptosis rather than by the generation of DNA damage." ], "offsets": [ [ 101, 1617 ] ] } ]

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[ { "id": "883eb35d-6f72-4dda-92d6-b53a75916d47", "type": "title", "text": [ "Molecular and clinical heterogeneity in CLCN7-dependent osteopetrosis: report of 20 novel mutations." ], "offsets": [ [ 0, 100 ] ] }, { "id": "26ef84ae-15ae-4078-ba01-dcd718083ddb", "type": "abstract", "text": [ "The "Osteopetroses" are genetic diseases whose clinical picture is caused by a defect in bone resorption by osteoclasts. Three main forms can be distinguished on the basis of severity, age of onset and means of inheritance: the dominant benign, the intermediate and the recessive severe form. While several genes have been involved in the pathogenesis of the different types of osteopetroses, the CLCN7 gene has drawn the attention of many researchers, as mutations within this gene are associated with very different phenotypes. We report here the characterization of 25 unpublished patients which has resulted in the identification of 20 novel mutations, including 11 missense mutations, 6 causing premature termination, 1 small deletion and 2 putative splice site defects. Careful analysis of clinical and molecular data led us to several conclusions. First, intermediate osteopetrosis is not homogeneous, since it can comprise both severe dominant forms with an early onset and recessive ones without central nervous system involvement. Second, the appropriateness of haematopoietic stem cell transplantation in CLCN7-dependent ARO patients has to be carefully evaluated and exhaustive CNS examination is strongly suggested, as transplantation can almost completely cure the disease in situations where no primary neurological symptoms are present. Finally, the analysis of this largest cohort of CLCN7-dependent ARO patients together with some ADO II families allowed us to draw preliminary genotype-phenotype correlations suggesting that haploinsufficiency is not the mechanism causing ADO II. The availability of biochemical assays to characterize ClC-7 function will help to confirm this hypothesis." ], "offsets": [ [ 101, 1818 ] ] } ]

[ { "id": "839900dd-cb6f-4470-af21-f779cde2bbbe", "type": "Gene", "text": [ "CLCN7" ], "offsets": [ [ 40, 45 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9a11880f-2ec9-4bd1-b36d-0068709f6ba9", "type": "Gene", "text": [ "CLCN7" ], "offsets": [ [ 508, 513 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "aee6fa87-437b-4a89-a5e2-c2fd74fb4bbf", "type": "Gene", "text": [ "CLCN7" ], "offsets": [ [ 1227, 1232 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ff35b217-16a9-4b35-82e3-febc140cc425", "type": "Gene", "text": [ "CLCN7" ], "offsets": [ [ 1512, 1517 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "318ff922-ccd3-480c-931b-8f56390f1149", "type": "FamilyName", "text": [ "ADO II" ], "offsets": [ [ 1560, 1566 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c320802d-9e67-45d7-873e-418a41a0da04", "type": "FamilyName", "text": [ "ADO II" ], "offsets": [ [ 1703, 1709 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a2a2c0ba-109d-4dc1-99e6-8e20dc315bbb", "type": "Gene", "text": [ "ClC-7" ], "offsets": [ [ 1766, 1771 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "6a95ae16-2d9b-461d-9fb9-185476221c38", "type": "title", "text": [ "Association and functional analyses of MEF2A as a susceptibility gene for premature myocardial infarction and coronary artery disease." ], "offsets": [ [ 0, 134 ] ] }, { "id": "ec8a84d0-9c36-4ba5-a7a5-c279407441bc", "type": "abstract", "text": [ "BACKGROUND: Mutations in the MEF2A gene, coding for a member of the myocyte enhancer factor 2 family of transcription factors, have been reported in patients with coronary artery disease and myocardial infarction (MI). In particular, a 21-bp deletion and 3 missense mutations were demonstrated either to reduce MEF2A transcriptional activity or to impair its nuclear translocation. However, the association of MEF2A with coronary artery disease/MI was not confirmed in other studies. We analyzed the role of MEF2A in the pathogenesis of MI in 2008 Italian patients with premature MI and in 2008 controls. METHODS AND RESULTS: Mutational screening of exon 8 (containing all so-far reported point mutations) disclosed 5 novel and 2 previously described missense mutations. Microsatellite genotyping and sequencing revealed the presence of the 21-bp deletion (located in exon 12) in 5 cases and in none of the controls. Functional studies on mutant proteins showed no alteration, neither in the transactivating properties (all mutants) nor in the nuclear localization (21-bp deletion). Furthermore, an association analysis performed using 3 microsatellites at the MEF2A locus showed no significant association with MI. These results were confirmed in a replication study performed on an independent Italian population with coronary artery disease. CONCLUSIONS: All together, our data do not support MEF2A as a susceptibility gene for coronary artery disease/MI in the Italian population." ], "offsets": [ [ 135, 1619 ] ] } ]

[ { "id": "5b13b57c-4634-4255-8fe0-076f722392ad", "type": "Gene", "text": [ "MEF2A" ], "offsets": [ [ 39, 44 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9ccc2fef-bab0-465b-8127-d5219a43f123", "type": "FamilyName", "text": [ "susceptibility gene" ], "offsets": [ [ 50, 69 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "57bd4212-51a8-4ea6-8bfa-beae3371a48c", "type": "Gene", "text": [ "MEF2A" ], "offsets": [ [ 164, 169 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "16f2a6fa-9c3f-4e55-9e78-530a7571a6c4", "type": "FamilyName", "text": [ "myocyte enhancer factor 2" ], "offsets": [ [ 203, 228 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "222b0e44-4009-46cb-829b-b550dcdc21f1", "type": "Gene", "text": [ "MEF2A" ], "offsets": [ [ 446, 451 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c647defe-b150-4ec3-adc4-50539cb3ef2c", "type": "Gene", "text": [ "MEF2A" ], "offsets": [ [ 545, 550 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "87c56197-1414-4754-98bb-5e893e336fb4", "type": "Gene", "text": [ "MEF2A" ], "offsets": [ [ 643, 648 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d546ac77-8047-4f21-8f5a-7fbd9c48d70b", "type": "Gene", "text": [ "MEF2A" ], "offsets": [ [ 1296, 1301 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d8c2b892-f304-4dc7-a89c-8a94a161a588", "type": "Gene", "text": [ "MEF2A" ], "offsets": [ [ 1531, 1536 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "eb623f0c-7d8d-43ed-9fb0-d91f63088a7d", "type": "FamilyName", "text": [ "susceptibility gene" ], "offsets": [ [ 1542, 1561 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "157928f4-33da-485c-9174-2ea2be077c48", "type": "title", "text": [ "Novel and recurrent p14 mutations in Italian familial melanoma." ], "offsets": [ [ 0, 63 ] ] }, { "id": "e13dd2ee-a516-428f-82b7-8ecc28e01220", "type": "abstract", "text": [ "CDKN2A and CDK4 are the only known high-penetrant genes conferring proneness to cutaneous melanoma. The CDKN2A locus consists of four exons and encodes several alternate transcripts, two of which are p16(INK4a) and p14(ARF), and originate from different open reading frames. Exon 1alpha is specific for p16(INK4a), while exon 1beta characterizes p14(ARF). Most CDKN2A mutations are located in exons 1alpha and 2, while exon 1beta variations have been identified in rare melanoma-prone pedigrees. In a previous study, we investigated 155 Italian melanoma cases, including 94 familial melanomas (FAMs) and 61 sporadic multiple primary melanomas (MPMs), for p16(INK4a)/CDK4 germline alterations and identified 15 p16(INK4a) and 1 CDK4 point mutations. In the present work, we extended our search to p14(ARF) mutations and CDKN2A deletions in the remaining samples. We identified the recurrent g.193+1G> A mutation in two FAM cases, while an additional pedigree displayed the previously undescribed variant g.161G> A. Multiplex ligation-dependent probe amplification (MLPA) screening for copy variations resulted negative in all cases. In Italy, the overall frequency of p14(ARF) mutations is 3.2% in FAM and 0% in sporadic MPM. Re-evaluation of our patients' cohort emphasizes that the chance of identifying CDKN2A/CDK4 mutations in FAM is mainly influenced by the number of affected family members and the presence of one or more MPM cases. Accordingly, mutation rate rises to 61% in selected cases. Further studies are expected in order to investigate CDKN2A rarer mutations, including atypical deletions and inherited epimutations." ], "offsets": [ [ 64, 1706 ] ] } ]

[ { "id": "2ab36437-a916-448c-b1ce-13a44822c5f1", "type": "Gene", "text": [ "p14" ], "offsets": [ [ 20, 23 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "de2e9b76-512f-4a28-8864-8f1f9ac4f5f0", "type": "Gene", "text": [ "CDKN2A" ], "offsets": [ [ 64, 70 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "11808f9a-dcee-4cfe-b380-f1cfce64ceba", "type": "Gene", "text": [ "CDK4" ], "offsets": [ [ 75, 79 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8977326d-74a3-4465-a8a9-a80c8306abe1", "type": "Gene", "text": [ "CDKN2A" ], "offsets": [ [ 168, 174 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2f5ddd01-f303-4352-9e6a-e7e3901dda92", "type": "Gene", "text": [ "p16" ], "offsets": [ [ 264, 267 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "30ac13a9-8560-4ac8-b549-1f4f8a854040", "type": "Gene", "text": [ "INK4a" ], "offsets": [ [ 268, 273 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "18f6e956-d3c0-4346-8d0b-4084bf0f0605", "type": "Gene", "text": [ "p14" ], "offsets": [ [ 279, 282 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7f59bb14-64f8-47c1-a109-f2e16fb96126", "type": "Gene", "text": [ "ARF" ], "offsets": [ [ 283, 286 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1feb7433-712a-4cf4-b4ca-ffc49bc7e47b", "type": "Gene", "text": [ "p16" ], "offsets": [ [ 367, 370 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2ef96872-f2b9-4d40-a6c8-cfac8a58fd43", "type": "Gene", "text": [ "INK4a" ], "offsets": [ [ 371, 376 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6052acbe-ce25-4683-8507-ebe3354b5c19", "type": "Gene", "text": [ "p14" ], "offsets": [ [ 410, 413 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e8bda6f0-e15e-46b9-a681-4da266a56944", "type": "Gene", "text": [ "ARF" ], "offsets": [ [ 414, 417 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "506ee65b-c8da-47cd-9a86-396152d1fb0b", "type": "Gene", "text": [ "CDKN2A" ], "offsets": [ [ 425, 431 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6ad28036-cbcc-4be9-a783-ea5708b3c174", "type": "Gene", "text": [ "p16" ], "offsets": [ [ 719, 722 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c2a647bd-2c23-4f44-8c99-97f7ff8f4fa5", "type": "Gene", "text": [ "INK4a" ], "offsets": [ [ 723, 728 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "399d4cdb-d516-416a-947a-53c4a630e7fa", "type": "Gene", "text": [ "CDK4" ], "offsets": [ [ 730, 734 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0a32cd55-abb9-4614-a67c-f5c09719dbaa", "type": "Gene", "text": [ "p16" ], "offsets": [ [ 774, 777 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9640cebe-cd28-49ea-b0c5-2435c41aa754", "type": "Gene", "text": [ "INK4a" ], "offsets": [ [ 778, 783 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4d77bd4e-b0ee-4a59-a123-4db0cd79b074", "type": "Gene", "text": [ "CDK4" ], "offsets": [ [ 791, 795 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "dd9d3969-6bad-4ce0-99f1-a30eafe108cb", "type": "Gene", "text": [ "p14" ], "offsets": [ [ 860, 863 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d344af3d-a5e7-4da0-aaa6-3bff6db6092c", "type": "Gene", "text": [ "ARF" ], "offsets": [ [ 864, 867 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0586788a-e1da-43b0-99e7-1029c21e3af1", "type": "Gene", "text": [ "CDKN2A" ], "offsets": [ [ 883, 889 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4849b46b-5ba2-4131-b7ed-d5795bb4a512", "type": "Gene", "text": [ "p14" ], "offsets": [ [ 1237, 1240 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fe2bc1b7-2a2e-45b3-ba97-753ab37fe3a1", "type": "Gene", "text": [ "ARF" ], "offsets": [ [ 1241, 1244 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "23973f04-9163-4cb8-aa44-bdfb1d57a2cf", "type": "Gene", "text": [ "CDKN2A" ], "offsets": [ [ 1380, 1386 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6bc75c9d-7500-48d2-8f53-66d57312ef1d", "type": "Gene", "text": [ "CDK4" ], "offsets": [ [ 1387, 1391 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6afdfda6-4455-45ef-b845-b3c9e6e7cb9f", "type": "Gene", "text": [ "CDKN2A" ], "offsets": [ [ 1626, 1632 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "337e2b3f-1004-4a95-aa16-89b4e3a0c757", "type": "title", "text": [ "Intellectual disability, midface hypoplasia, facial hypotonia, and Alport syndrome are associated with a deletion in Xq22.3." ], "offsets": [ [ 0, 124 ] ] }, { "id": "639b25cf-5d75-480d-9df6-1e72a35c3587", "type": "abstract", "text": [ "Alport syndrome with intellectual disability (ID) is a contiguous gene deletion syndrome involving several genes on Xq22.3 including COL4A5 and ACSL4. We report on a family with two males with this disorder and a Xq22.3 deletion. Fluorescent in situ hybridization and genomic analyses mapped the deletion region to between exon 1 of COL4A5 and exon 12 of ACSL4. The patients' mother has microscopic hematuria and was found to be heterozygous for the Xq22.3 deletion. Analysis using reverse transcription polymerase chain reaction of lymphoblastoid cell line RNA from an affected male in the family revealed a stable chimeric transcript with the ACSL4 exons 13-17 replaced by a cryptic exon from intron 1 of the COL4A5 gene. A truncated 54 kDa protein was predicted from this transcript but Western blot analysis and ACSL4 enzyme assay both showed functional nullisomy of ACSL4. We also compared the clinical features of the family with three previously reported families with the ACSL4 gene deletion and found that ID with absent or severely delayed speech, midface hypoplasia, and facial hypotonia are consistent features observed in the absence of ACSL4 gene." ], "offsets": [ [ 125, 1291 ] ] } ]

[ { "id": "a2e9fa70-3df1-4895-b572-506cd822ac02", "type": "Gene", "text": [ "COL4A5" ], "offsets": [ [ 258, 264 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8a0d1b16-6659-4d4f-b0ae-d141be4a4fac", "type": "Gene", "text": [ "ACSL4" ], "offsets": [ [ 269, 274 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "140774bc-5bdc-4315-a87b-772069d40d44", "type": "Gene", "text": [ "COL4A5" ], "offsets": [ [ 458, 464 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "42cb4b93-8aef-40b5-9706-44d738acb068", "type": "Gene", "text": [ "ACSL4" ], "offsets": [ [ 480, 485 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ce06eb5a-4760-4a4c-93d5-87020dea11f8", "type": "Gene", "text": [ "ACSL4" ], "offsets": [ [ 775, 780 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c02e4536-8d64-4587-8ba4-2f4269149005", "type": "Gene", "text": [ "COL4A5" ], "offsets": [ [ 841, 847 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2a05ecbf-ed77-4240-b020-3ce6130b17ec", "type": "Gene", "text": [ "ACSL4" ], "offsets": [ [ 946, 951 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "353916b0-77d9-4c48-bab1-0705160acc61", "type": "Gene", "text": [ "ACSL4" ], "offsets": [ [ 1001, 1006 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7ec4c030-419e-4a96-b941-880a7980e0cd", "type": "Gene", "text": [ "ACSL4" ], "offsets": [ [ 1110, 1115 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ee999351-cb23-4dc3-a82e-89271414c7af", "type": "Gene", "text": [ "ACSL4" ], "offsets": [ [ 1280, 1285 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "2713f0c6-1593-401e-8a64-89f4e7a875db", "type": "title", "text": [ "Potential liability of reproductive endocrinologists for high order multiple gestation." ], "offsets": [ [ 0, 87 ] ] }, { "id": "eebabda5-4ea0-4f62-97f2-aab6d596cdb8", "type": "abstract", "text": [ "BACKGROUND: In light of the recent octuplet birth and the accompanying intensive media coverage, there has been much attention on high order multiple births resulting from assisted reproductive technology. OBJECTIVES: The purpose of this commentary is to review 1) the relative contribution of ART to high order multiple gestation and its impact on infant morbidity, mortality, and health care dollar loss; 2) American Society of Reproductive Medicine's guidelines for the number of embryos transferred in ART; and 3) how reproductive endocrinologists can lessen their exposure to litigation by following the ASRM guidelines for the number of embryos transferred and documenting proper informed consent in the medical records. RECOMMENDATIONS: In situations in which the number of embryos transferred is in excess of the ASRM guidelines, justification for deviating from the ASRM guidelines should be justifiable and documented in the medical records." ], "offsets": [ [ 88, 1044 ] ] } ]

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[ { "id": "63dd6de4-1cc0-4719-889f-a49289d778e4", "type": "title", "text": [ "The human AHR: identification of single nucleotide polymorphisms from six ethnic populations." ], "offsets": [ [ 0, 93 ] ] }, { "id": "820aef7b-cc9a-4e95-9fc1-eca9f0c286ed", "type": "abstract", "text": [ "BACKGROUND: The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and related dioxin-like chemicals are mediated through binding-dependent activation of the cytosolic aryl hydrocarbon receptor (AHR). The human AHR is a low-affinity receptor relative to most rodents, but some reports suggest that there may be individuals with polymorphic high-affinity receptors, thereby possibly increasing the sensitivity to dioxins in such people. METHODS: Although no polymorphisms have been reported in the ligand binding region of the AHR in the over 100 reported sequences, we sequenced 108 additional human AHR genes in an effort to further identify single single nucleotide polymorphisms (SNPs) within the open reading frames of the AHR locus. The DNA was sequenced from six ethnic populations that included Japanese, Chinese, European/Caucasian, African-American, South East Asian, and Hispanic. RESULTS: Six exonic SNPs were identified; four had been described as previously reported and two seem to be novel. Four of the SNPs identified lead to amino acid changes in the AHR protein and two of the SNPs lead to synonymous substitutions. An additional four SNPs have been reported elsewhere that were not identified in the current analysis. With these new sequences, more than 200 human AHR gene sequences have been analyzed for SNPs. CONCLUSION: The results indicate a very limited presence of polymorphisms in the core ligand binding region of the human AHR. Other regions, such as the transactivation domain, seem to be slightly more polymorphic in the human population and the impact on functionality should be further examined." ], "offsets": [ [ 94, 1718 ] ] } ]

[ { "id": "7637b51c-caaa-415b-a000-e5fc3fa70c44", "type": "Gene", "text": [ "AHR" ], "offsets": [ [ 10, 13 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "242db04a-a623-4bd9-8927-193e26c5ac35", "type": "Gene", "text": [ "aryl hydrocarbon receptor" ], "offsets": [ [ 258, 283 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b3a66bde-3084-405b-bab0-92982eb36f75", "type": "Gene", "text": [ "AHR" ], "offsets": [ [ 285, 288 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "26ec77a5-7402-4c76-b4fe-db10d1fa1677", "type": "Gene", "text": [ "AHR" ], "offsets": [ [ 301, 304 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9cdc7e5e-9121-458c-b168-312904eb966e", "type": "Gene", "text": [ "AHR" ], "offsets": [ [ 616, 619 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "422ef786-c53b-4b5b-ae7c-e16692064389", "type": "Gene", "text": [ "AHR" ], "offsets": [ [ 690, 693 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f92bf5e8-342c-4f3f-82b0-c1f9b5ba0bcb", "type": "Gene", "text": [ "AHR" ], "offsets": [ [ 817, 820 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a886649f-ebc4-4e2d-948d-2fb3908c496c", "type": "Gene", "text": [ "AHR" ], "offsets": [ [ 1158, 1161 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3242ba55-86a4-4ef9-9bc4-1c7f3004b1f4", "type": "Gene", "text": [ "AHR" ], "offsets": [ [ 1373, 1376 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b59f8857-51bb-4a1c-9c8b-7f02df4e5920", "type": "Gene", "text": [ "AHR" ], "offsets": [ [ 1542, 1545 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "00de1316-9b2d-43d0-a9fa-1837bc8898f4", "type": "title", "text": [ "Vitamin E reduces cardiovascular disease in individuals with diabetes mellitus and the haptoglobin 2-2 genotype." ], "offsets": [ [ 0, 112 ] ] }, { "id": "8ec69cf2-e61d-4044-9d3f-e80d2e770b55", "type": "abstract", "text": [ "AIMS: Individuals with both diabetes mellitus (DM) and the Haptoglobin (Hp) 2-2 genotype are at increased risk of cardiovascular disease. As the antioxidant function of the Hp 2-2 protein is impaired, we sought to test the pharmacogenomic hypothesis that antioxidant vitamin E supplementation would provide cardiovascular protection to Hp 2-2 DM individuals. MATERIALS & METHODS: We determined the Hp genotype on DM participants from two trials (HOPE and ICARE) and assessed the effect of vitamin E by Hp genotype on their common prespecified outcome, the composite of stroke, myocardial infarction and cardiovascular death. Data was analyzed with a fixed-effect model. These results were input into a simulation model, the Evidence Based Medicine Integrator, in order to estimate their long-term implications in a real-world population from Kaiser Permanente (CA, USA). RESULTS: Meta-analysis of the two trials demonstrated a significant overall reduction in the composite end point in Hp 2-2 DM individuals with vitamin E (odds ratio: 0.58; 95% CI: 0.40-0.86; p = 0.006). There was a statistically significant interaction between the Hp genotype and vitamin E on the composite end point. In these trials, Hp typing of 69 DM individuals and treating those with the Hp 2-2 with vitamin E prevented one myocardial infarct, stroke or cardiovascular death. Lifelong administration of vitamin E to Hp 2-2 DM individuals in the Kaiser population would increase their life expectancy by 3 years. CONCLUSION: A pharmacogenomic strategy of screening DM individuals for the Hp genotype and treating those with Hp 2-2 with vitamin E appears to be highly clinically effective." ], "offsets": [ [ 113, 1782 ] ] } ]

[ { "id": "8f253500-1fe8-4a80-8da3-30a091a63ad5", "type": "Gene", "text": [ "haptoglobin" ], "offsets": [ [ 87, 98 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "afedf9f5-f98f-4953-ab1a-989e82434265", "type": "Gene", "text": [ "Haptoglobin" ], "offsets": [ [ 172, 183 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "53ca84c9-fb83-4e7b-b25f-c12b798eec89", "type": "Gene", "text": [ "Hp" ], "offsets": [ [ 185, 187 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e3c16069-0998-48b2-b8b2-1b3aa63928bf", "type": "Gene", "text": [ "Hp" ], "offsets": [ [ 286, 288 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a2b73c2d-ed5a-4ea9-897e-d772ba61cd9d", "type": "Gene", "text": [ "Hp" ], "offsets": [ [ 449, 451 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "43f59855-3c1e-48e2-8caf-9c859d8f7008", "type": "Gene", "text": [ "Hp" ], "offsets": [ [ 515, 517 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "931ec515-14a4-4aef-b5a4-9d977bd81927", "type": "Gene", "text": [ "Hp" ], "offsets": [ [ 619, 621 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d0b290bd-4c02-47bf-814f-9992dd561012", "type": "Gene", "text": [ "Hp" ], "offsets": [ [ 1104, 1106 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "02ce88ad-7df7-4141-9490-c1310ccd80ec", "type": "Gene", "text": [ "Hp" ], "offsets": [ [ 1253, 1255 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c6a3ea97-837d-4212-ba42-5d9b378458f7", "type": "Gene", "text": [ "Hp" ], "offsets": [ [ 1324, 1326 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "74f3c47b-fdfd-4677-aea4-2625af7a49a2", "type": "Gene", "text": [ "Hp" ], "offsets": [ [ 1383, 1385 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "29222a06-9d6b-402d-86cb-0463a16710c6", "type": "Gene", "text": [ "Hp" ], "offsets": [ [ 1511, 1513 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c7b7c20e-b94e-4c0e-923a-f2311b3c92c5", "type": "Gene", "text": [ "Hp" ], "offsets": [ [ 1682, 1684 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8b4e860e-36e7-4028-ae99-8e9e80fe7f55", "type": "Gene", "text": [ "Hp" ], "offsets": [ [ 1718, 1720 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "bd09cfad-d708-4bee-ad99-ed3466266158", "type": "title", "text": [ "Effect of the abrogation of TGF-beta1 by antisense oligonucleotides on the expression of TGF-beta-isoforms and their receptors I and II in isolated fibroblasts from keloid scars." ], "offsets": [ [ 0, 178 ] ] }, { "id": "35d002d0-2b34-41b8-ba05-cab5f85bbe95", "type": "abstract", "text": [ "Disequilibrium of dermal wound repair can result in continued accumulation of ECM and excessive scar formation. In susceptible genetically predisposed individuals, keloid formation can be observed. Keloid disease represents a benign dermal fibroproliferative tumor that is unique to humans. TGF-beta is known to play a key role in the pathogenesis of this disease which is still not fully understood. The isoforms TGF-beta1 and TGF-beta2 have profibrotic properties, whereas TGF-beta3 may have antifibrotic functions. TGF-beta exerts its influence by binding to type I and type II TGF-beta receptors, thereby forming a complex and activating specific downstream effector molecules. The aim of this study was to investigate the effect of TGF-beta1 targeting by antisense oligonucleotides on the RNA synthesis and protein expression of TGF-beta isoforms and their receptors in keloid-derived fibroblasts. In tissue samples with normal fibroblasts (NFs) serving as control samples, expression of TGF-beta1 and -beta2 was decreased when compared to keloid fibroblasts (KFs), while expression of TGF-beta3 and of TGF-betaRII was significantly higher in NFs. In the ELISA assay, abrogation of TGF-beta1 led to a significant decrease in TGF-beta1 and -beta2 (p<0.05). Expression of TGF-beta2 mRNA was reduced. Expression of TGF-beta3 mRNA revealed contrary patterns in KFs from different patients while expression of TGF-betaRI was found to be equal during the measurement period. TGF-betaRII mRNA expression was increased after 48 and 72 h respectively. There is growing evidence for a regulatory mechanism between TGF-beta1 and its receptors. Our findings support this theory by suggesting interrelations between the different TGF-beta isoforms and their receptors. Abnormal response of KFs to TGF-betamight reflect a modification in the regulatory pathway that occurs at the receptor level or during intracellular trans-duction. Improving the understanding of TGF-beta in keloid disease could lead to the development of clinically useful therapeutic modalities for treatment of keloid disease or even allow identification of preventive strategies." ], "offsets": [ [ 179, 2325 ] ] } ]

[ { "id": "35dad121-8992-4292-831b-c2cfd5b9a99c", "type": "Gene", "text": [ "TGF-beta1" ], "offsets": [ [ 28, 37 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "81ae369e-6de1-4242-b052-1a1183e2e042", "type": "Gene", "text": [ "TGF-beta-isoforms and their receptors I and II" ], "offsets": [ [ 89, 135 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9e4c5f69-28df-45c9-b4a1-27285b4b8baf", "type": "FamilyName", "text": [ "TGF-beta" ], "offsets": [ [ 470, 478 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c736348e-7409-4c60-8f1d-dfc8366708ab", "type": "Gene", "text": [ "TGF-beta1" ], "offsets": [ [ 593, 602 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e791fb86-9012-4707-b2f0-567607676317", "type": "Gene", "text": [ "TGF-beta2" ], "offsets": [ [ 607, 616 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "30f68321-d609-4dac-9497-53a6ea8758ec", "type": "Gene", "text": [ "TGF-beta3" ], "offsets": [ [ 654, 663 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "176a9285-3272-4296-91d0-34a0c3218cc9", "type": "FamilyName", "text": [ "TGF-beta" ], "offsets": [ [ 697, 705 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ed81311e-312b-487c-b6d6-6ed85d5c6d0c", "type": "Gene", "text": [ "type I and type II TGF-beta receptors" ], "offsets": [ [ 741, 778 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "948a1cf0-a552-4884-8297-6899d6880c05", "type": "Gene", "text": [ "TGF-beta1" ], "offsets": [ [ 916, 925 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5e3ae135-e296-42b3-a2eb-75fa2add63cc", "type": "FamilyName", "text": [ "TGF-beta" ], "offsets": [ [ 1013, 1021 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "76a4fe30-9b6c-4d30-8196-a367dc7fd5d4", "type": "Gene", "text": [ "TGF-beta1 and -beta2" ], "offsets": [ [ 1172, 1192 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "59c59bcd-5fbc-4a8d-a926-853420c884a6", "type": "Gene", "text": [ "TGF-beta3" ], "offsets": [ [ 1270, 1279 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6d89d83e-8a60-4a4f-85ef-328f7d003529", "type": "Gene", "text": [ "TGF-betaRII" ], "offsets": [ [ 1287, 1298 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1dbe8b8d-f2af-4d2f-9ca6-89834ee80fc1", "type": "Gene", "text": [ "TGF-beta1" ], "offsets": [ [ 1366, 1375 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fda6fb91-7659-434d-81ce-daa245744d12", "type": "Gene", "text": [ "TGF-beta1 and -beta2" ], "offsets": [ [ 1409, 1429 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c62a5525-244b-4c51-a597-c267e0ea47ba", "type": "Gene", "text": [ "TGF-beta2" ], "offsets": [ [ 1457, 1466 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8be2988c-b408-4b42-b1aa-103b6a43eaef", "type": "Gene", "text": [ "TGF-beta3" ], "offsets": [ [ 1499, 1508 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "bd617e46-879e-43fe-84c6-af8f31d2f0fd", "type": "Gene", "text": [ "TGF-betaRI" ], "offsets": [ [ 1592, 1602 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d21f688e-702d-4132-91db-faf133ed1330", "type": "Gene", "text": [ "TGF-betaRII" ], "offsets": [ [ 1656, 1667 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "69887fee-e7c4-4865-ab35-2beb21f94278", "type": "Gene", "text": [ "TGF-beta1" ], "offsets": [ [ 1791, 1800 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "657b779a-f4ea-45a5-b455-80f8d46fb396", "type": "FamilyName", "text": [ "TGF-beta" ], "offsets": [ [ 1904, 1912 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1347b34d-6378-4e69-90fa-52dcb13642c9", "type": "FamilyName", "text": [ "TGF-beta" ], "offsets": [ [ 1971, 1979 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ce41eeae-99e6-4c34-a68e-7fed8c87b485", "type": "FamilyName", "text": [ "TGF-beta" ], "offsets": [ [ 2138, 2146 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "aae4d12e-bf9b-4928-9bae-e9695902bc88", "type": "title", "text": [ "NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype." ], "offsets": [ [ 0, 75 ] ] }, { "id": "703edd9c-b142-4e08-853a-44719a68f798", "type": "abstract", "text": [ "In 5-10% of patients, neurofibromatosis type 1 (NF1) results from microdeletions that encompass the entire NF1 gene and a variable number of flanking genes. Two recurrent microdeletion types are found in most cases, with microdeletion breakpoints located in paralogous regions flanking NF1 (proximal NF1-REP-a and distal NF1-REP-c for the 1.4 Mb type-1 microdeletion, and SUZ12 and SUZ12P for the 1.2 Mb type-2 microdeletion). A more severe phenotype is usually associated with NF1 microdeletion patients than in those with intragenic mutations. We characterized NF1 microdeletions in 70 unrelated NF1 microdeleted patients using a high-resolution NF1 custom array comparative genomic hybridization (CGH). Genotype-phenotype correlations were studied in 58 of these microdeletion patients and compared to 389 patients with intragenic truncating NF1 mutations and phenotyped in the same standardized way. Our results confirmed in an unbiased manner the existence of a contiguous gene syndrome with a significantly higher incidence of learning disabilities and facial dysmorphism in microdeleted patients compared to patients with intragenic NF1 mutations. Microdeleted NF1 patients also showed a trend toward significance for childhood overgrowth. High-resolution array-CGH identified a new recurrent approximately 1.0 Mb microdeletion type, designated as type-3, with breakpoints in the paralogous regions middle NF1-REP-b and distal NF1-REP-c." ], "offsets": [ [ 76, 1520 ] ] } ]

[ { "id": "097a0c92-feb8-4c61-a875-ef613f2b0cf5", "type": "Gene", "text": [ "NF1" ], "offsets": [ [ 0, 3 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fe77e65c-49b9-4171-8ef5-8c5498d2613c", "type": "Gene", "text": [ "neurofibromatosis type 1" ], "offsets": [ [ 22, 46 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "eaceaf9f-699d-49f1-bd8c-5707d39908cf", "type": "Gene", "text": [ "neurofibromatosis type 1" ], "offsets": [ [ 98, 122 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3af7a438-fccd-414a-ac58-9e59b4126eb7", "type": "Gene", "text": [ "NF1" ], "offsets": [ [ 124, 127 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fb49a2c2-b466-466c-ba33-8e54a464f59e", "type": "Gene", "text": [ "NF1" ], "offsets": [ [ 183, 186 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0a33e774-d8f1-43d8-bf9a-fecf1fac242c", "type": "Gene", "text": [ "NF1" ], "offsets": [ [ 362, 365 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2b51ae52-d56f-4e61-884e-3a82a659c08f", "type": "Gene", "text": [ "NF1" ], "offsets": [ [ 376, 379 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8028e94c-57bd-48d7-b194-410aeb7211a9", "type": "Gene", "text": [ "NF1" ], "offsets": [ [ 397, 400 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "31cc1770-99ea-47da-b345-34906ce6c850", "type": "Gene", "text": [ "SUZ12" ], "offsets": [ [ 448, 453 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9f3bfcf7-5bc8-41d1-a1a9-23614fff8666", "type": "Gene", "text": [ "SUZ12P" ], "offsets": [ [ 458, 464 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4e4a1221-568e-43b7-8c55-329b1e92b75c", "type": "Gene", "text": [ "NF1" ], "offsets": [ [ 554, 557 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0eb48b3c-6467-40c3-a707-99ef13738c06", "type": "Gene", "text": [ "NF1" ], "offsets": [ [ 639, 642 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0dc17f95-1f4b-41fd-b4ff-d78c8cbb7919", "type": "Gene", "text": [ "NF1" ], "offsets": [ [ 674, 677 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "10748efc-fe3a-4202-a9c7-4c89e4e21916", "type": "Gene", "text": [ "NF1" ], "offsets": [ [ 724, 727 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3fbafbe0-f387-4c45-982d-e3cb8507b3c4", "type": "Gene", "text": [ "NF1" ], "offsets": [ [ 921, 924 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4b580e27-19fd-402b-944f-51b207199ee3", "type": "Gene", "text": [ "NF1" ], "offsets": [ [ 1216, 1219 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "92122cdb-2134-4faf-ba72-8582ebd3f41d", "type": "Gene", "text": [ "NF1" ], "offsets": [ [ 1244, 1247 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "22cb513a-c6ca-421a-9205-971c479f1497", "type": "Gene", "text": [ "NF1" ], "offsets": [ [ 1489, 1492 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1d10eaf0-7588-4934-9fa7-fa4d9e9f33a1", "type": "Gene", "text": [ "NF1" ], "offsets": [ [ 1510, 1513 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "58647f29-079b-4ff4-9159-8d768125735e", "type": "title", "text": [ "Sex-differential genetic effect of phosphodiesterase 4D (PDE4D) on carotid atherosclerosis." ], "offsets": [ [ 0, 91 ] ] }, { "id": "7b504885-bfd2-45d5-9874-ad01e1546bcf", "type": "abstract", "text": [ "BACKGROUND: The phosphodiesterase 4D (PDE4D) gene was reported as a susceptibility gene to stroke. The genetic effect might be attributed to its role in modulating the atherogenic process in the carotid arteries. Using carotid intima-media thickness (IMT) and plaque index as phenotypes, the present study sought to determine the influence of this gene on subclinical atherosclerosis. METHODS: Carotid ultrasonography was performed on 1013 stroke-free subjects who participated in the health screening programs (age 52.6 +/- 12.2; 47.6% men). Genotype distribution was compared among the high-risk (plaque index > or = 4), low-risk (index = 1-3), and reference (index = 0) groups. We analyzed continuous IMT data and further dichotomized IMT data using mean plus one standard deviation as the cutoff level. Because the plaque prevalence and IMT values displayed a notable difference between men and women, we carried out sex-specific analyses in addition to analyzing the overall data. Rs702553 at the PDE4D gene was selected because it conferred a risk for young stroke in our previous report. Previous young stroke data (190 cases and 211 controls) with an additional 532 control subjects without ultrasonic data were shown as a cross-validation for the genetic effect. RESULTS: In the overall analyses, the rare homozygote of rs702553 led to an OR of 3.1 (p = 0.034) for a plaque index > or = 4. When subjects were stratified by sex, the genetic effect was only evident in men but not in women. Comparing male subjects with plaque index > or = 4 and those with plaque index = 0, the TT genotype was over-represented (27.6% vs. 13.4%, p = 0.008). For dichotomized IMT data in men, the TT genotype had an OR of 2.1 (p = 0.032) for a thicker IMT at the common carotid artery compared with the (AA + AT) genotypes. In women, neither IMT nor plaque index was associated with rs702553. Similarly, SNP rs702553 was only significant in young stroke men (OR = 1.8, p = 0.025) but not in women (p = 0.27). CONCLUSIONS: The present study demonstrates a sex-differential effect of PDE4D on IMT, plaque index and stroke, which highlights its influence on various aspects of atherogenesis." ], "offsets": [ [ 92, 2279 ] ] } ]

[ { "id": "e7ab80b4-f3df-4678-a90c-609bfc8d9697", "type": "Gene", "text": [ "phosphodiesterase 4D" ], "offsets": [ [ 35, 55 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "dd6597cb-dcfe-43b8-b15e-8d927cc3b124", "type": "Gene", "text": [ "PDE4D" ], "offsets": [ [ 57, 62 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "51e189ce-fcdf-4caf-9766-872ccd052e2e", "type": "Gene", "text": [ "phosphodiesterase 4D" ], "offsets": [ [ 108, 128 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8b4b60fa-546b-4f0e-bd5c-1fc17ac370d0", "type": "Gene", "text": [ "PDE4D" ], "offsets": [ [ 130, 135 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "95f96ea1-01e9-487e-a706-581489432dc6", "type": "Gene", "text": [ "PDE4D" ], "offsets": [ [ 1097, 1102 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "affc9cec-c59d-464b-b1b9-bc684e2eb7af", "type": "Gene", "text": [ "PDE4D" ], "offsets": [ [ 2173, 2178 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "5a2ebb38-9d94-4432-b19d-db6688a59b4d", "type": "title", "text": [ "Identification of lipid droplet-associated proteins in the formation of macrophage-derived foam cells using microarrays." ], "offsets": [ [ 0, 120 ] ] }, { "id": "a1909550-3cdf-48f4-a44c-03f5ef41b0f5", "type": "abstract", "text": [ "A large number of macrophage-derived foam cells stores excessive neutral lipids in intracellular droplets, and plays a major role during the development of atherosclerosis. The formation and catabolism of intracellular lipid droplets (LDs) are regulated by LD-associated proteins, a group of proteins which are located on the surface of LDs and regulate the formation, morphology and lipolysis of LDs. In order to illustrate the function of LD-associated proteins during the process of atherosclerosis, the foam cell model is induced by oxidized low-density lipoprotein (ox-LDL) in macrophages originated from the THP-1 cell line, and cDNA microarrays are used to monitor the gene expression profiles of LD-associated proteins. Gene expression data show that 2% of changed genes are lipid binding genes during the transformation of foam cells. The major candidate genes, the cell death-inducing DFF45-like effector (CIDE) family and Perilipin, Adipophilin, and TIP47 (PAT) family, have different alterations during the formation of foam cells. CIDEB, CIDEC, Adipophilin, S3-12 and LSDP5 were up-regulated, while TIP47 was down-regulated. There was no significant change in CIDEA and Perilipin. These results were confirmed by real-time PCR and immunoblotting. This study presents a comprehensive analysis of the gene expression of LD-associated proteins during the differentiation of human foam cells, which may play an important role in the process of atherosclerosis." ], "offsets": [ [ 121, 1590 ] ] } ]

[ { "id": "7dd107f7-ab73-4215-a114-19d869986aee", "type": "FamilyName", "text": [ "lipid droplet-associated proteins" ], "offsets": [ [ 18, 51 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e84eff8a-f207-4f6e-b18e-990ea77629a3", "type": "FamilyName", "text": [ "LD-associated proteins" ], "offsets": [ [ 378, 400 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "accedb52-39de-48fb-937c-a48300860a27", "type": "FamilyName", "text": [ "LD-associated proteins" ], "offsets": [ [ 562, 584 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4ca002c5-692f-4c02-9aa8-b159f49e2991", "type": "FamilyName", "text": [ "LD-associated proteins" ], "offsets": [ [ 825, 847 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e70d75d7-78fb-4eff-b8b2-170e51121fce", "type": "FamilyName", "text": [ "lipid binding genes" ], "offsets": [ [ 904, 923 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "85f075ef-8c00-4123-ba71-9ef86a88b058", "type": "FamilyName", "text": [ "cell death-inducing DFF45-like effector" ], "offsets": [ [ 996, 1035 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d7ce6e17-593f-4105-86c6-e860491564f2", "type": "FamilyName", "text": [ "CIDE" ], "offsets": [ [ 1037, 1041 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "406b70b3-5fa8-48fd-b5fe-34501c33158f", "type": "Gene", "text": [ "Perilipin" ], "offsets": [ [ 1054, 1063 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4e5b7a86-2c47-42dd-96f1-66926f2685db", "type": "Gene", "text": [ "Adipophilin" ], "offsets": [ [ 1065, 1076 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d505e895-6e33-4bc9-a4bc-1a3cc5809757", "type": "Gene", "text": [ "TIP47" ], "offsets": [ [ 1082, 1087 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3a5378b5-794d-4dc3-85b7-f00a844e8bdd", "type": "Gene", "text": [ "PAT" ], "offsets": [ [ 1089, 1092 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c75766b6-0f1e-46d4-9425-0b4ac2502479", "type": "Gene", "text": [ "CIDEB" ], "offsets": [ [ 1165, 1170 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0fbed68b-bd53-4660-968f-d286ddcfcdf7", "type": "Gene", "text": [ "CIDEC" ], "offsets": [ [ 1172, 1177 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "73d83b0a-eb03-4f3f-b2f5-9935c9d41400", "type": "Gene", "text": [ "Adipophilin" ], "offsets": [ [ 1179, 1190 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8666abb7-f2df-48e7-b3d4-b8679f43571e", "type": "Gene", "text": [ "S3-12" ], "offsets": [ [ 1192, 1197 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "21efa3a3-4927-4204-9f9e-4e6045b2ef9e", "type": "Gene", "text": [ "LSDP5" ], "offsets": [ [ 1202, 1207 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "35495ec6-2188-45b2-9374-173294834fad", "type": "Gene", "text": [ "TIP47" ], "offsets": [ [ 1233, 1238 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "37e4062b-b09d-4756-b11d-aab99b3022b1", "type": "Gene", "text": [ "CIDEA" ], "offsets": [ [ 1294, 1299 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e3caf810-6e60-490d-82d0-1221f59288e8", "type": "Gene", "text": [ "Perilipin" ], "offsets": [ [ 1304, 1313 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d234d3f7-732b-4d9b-9f59-72d3d881950c", "type": "FamilyName", "text": [ "LD-associated proteins" ], "offsets": [ [ 1452, 1474 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "6ced8882-1eb8-4e3f-85f6-7737feca1b78", "type": "title", "text": [ "Genomic characterization of large rearrangements of the LDLR gene in Czech patients with familial hypercholesterolemia." ], "offsets": [ [ 0, 119 ] ] }, { "id": "52c73b9b-3573-4a18-b0a0-0c20dc1b9e4b", "type": "abstract", "text": [ "BACKGROUND: Mutations in the LDLR gene are the most frequent cause of Familial hypercholesterolemia, an autosomal dominant disease characterised by elevated concentrations of LDL in blood plasma. In many populations, large genomic rearrangements account for approximately 10% of mutations in the LDLR gene. METHODS: DNA diagnostics of large genomic rearrangements was based on Multiple Ligation dependent Probe Amplification (MLPA). Subsequent analyses of deletion and duplication breakpoints were performed using long-range PCR, PCR, and DNA sequencing. RESULTS: In set of 1441 unrelated FH patients, large genomic rearrangements were found in 37 probands. Eight different types of rearrangements were detected, from them 6 types were novel, not described so far. In all rearrangements, we characterized their exact extent and breakpoint sequences. CONCLUSIONS: Sequence analysis of deletion and duplication breakpoints indicates that intrachromatid non-allelic homologous recombination (NAHR) between Alu elements is involved in 6 events, while a non-homologous end joining (NHEJ) is implicated in 2 rearrangements. Our study thus describes for the first time NHEJ as a mechanism involved in genomic rearrangements in the LDLR gene." ], "offsets": [ [ 120, 1354 ] ] } ]

[ { "id": "3ef4406a-e7ef-4480-9252-499ba2177157", "type": "Gene", "text": [ "LDLR" ], "offsets": [ [ 56, 60 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3b30ee49-6d81-43e5-82bf-75f75ef035cb", "type": "Gene", "text": [ "LDLR" ], "offsets": [ [ 149, 153 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "789bbef3-c920-4059-8d5e-fbe9c784e985", "type": "Gene", "text": [ "LDLR" ], "offsets": [ [ 416, 420 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d10cbe48-45ea-4527-9c20-2da28bc25c81", "type": "Gene", "text": [ "LDLR" ], "offsets": [ [ 1344, 1348 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "2404b2ae-2ec8-43d1-bd95-28543d1c6939", "type": "title", "text": [ "Loss of corneodesmosin leads to severe skin barrier defect, pruritus, and atopy: unraveling the peeling skin disease." ], "offsets": [ [ 0, 117 ] ] }, { "id": "77634c2c-5fab-4112-a2fb-1849ed6ea202", "type": "abstract", "text": [ "Generalized peeling skin disease is an autosomal-recessive ichthyosiform erythroderma characterized by lifelong patchy peeling of the skin. After genome-wide linkage analysis, we have identified a homozygous nonsense mutation in CDSN in a large consanguineous family with generalized peeling skin, pruritus, and food allergies, which leads to a complete loss of corneodesmosin. In contrast to hypotrichosis simplex, which can be associated with specific dominant CDSN mutations, peeling skin disease is characterized by a complete loss of CDSN expression. The skin phenotype is consistent with a recent murine Cdsn knockout model. Using three-dimensional human skin models, we demonstrate that lack of corneodesmosin causes an epidermal barrier defect supposed to account for the predisposition to atopic diseases, and we confirm the role of corneodesmosin as a decisive epidermal adhesion molecule. Therefore, peeling skin disease will represent a new model disorder for atopic diseases, similarly to Netherton syndrome and ichthyosis vulgaris in the recent past." ], "offsets": [ [ 118, 1182 ] ] } ]

[ { "id": "99d5e591-a944-46f7-90f8-dfbb3e8bc0f2", "type": "Gene", "text": [ "corneodesmosin" ], "offsets": [ [ 8, 22 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b3c01d3c-e60d-4bed-b1ec-0898498bf8c5", "type": "Gene", "text": [ "CDSN" ], "offsets": [ [ 347, 351 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "abbef419-0375-4c31-a01a-1a385f9643f8", "type": "Gene", "text": [ "corneodesmosin" ], "offsets": [ [ 480, 494 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4c7c60c3-8b64-463e-b462-96092fff2420", "type": "Gene", "text": [ "CDSN" ], "offsets": [ [ 581, 585 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "724887f3-ce70-44d6-9ced-df4f9b7657eb", "type": "Gene", "text": [ "CDSN" ], "offsets": [ [ 657, 661 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "08876432-13b3-4012-b306-cdcf0cef9779", "type": "Gene", "text": [ "Cdsn" ], "offsets": [ [ 728, 732 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a16611f5-bbb1-47bb-82d0-e9c144da9465", "type": "Gene", "text": [ "corneodesmosin" ], "offsets": [ [ 820, 834 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0344116b-bccf-4354-94dc-09b44875bb22", "type": "Gene", "text": [ "corneodesmosin" ], "offsets": [ [ 960, 974 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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