Brizape/tmvar_split_0404 · Datasets at Hugging Face

id stringlengths 8 8	tokens list	ner_tags list	texts stringlengths 0 2.64k
22016685	[ "A", "novel", "missense", "mutation", "Asp506Gly", " ", "in", "Exon", "13", "of", "the", "F11", "gene", "in", "an", "asymptomatic", "Korean", "woman", "with", "mild", "factor", "XI", "deficiency." ]	[ 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	A novel missense mutation Asp506Gly in Exon 13 of the F11 gene in an asymptomatic Korean woman with mild factor XI deficiency.
22016685	[ "Factor", "XI", "(FXI)", "deficiency", "is", "a", "rare", "autosomal", "recessive", "coagulation", "disorder", "most", "commonly", "found", "in", "Ashkenazi", "and", "Iraqi", "Jews,", "but", "it", "is", "also", "found", "in", "other", "ethnic", "groups.", "It"...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	Factor XI (FXI) deficiency is a rare autosomal recessive coagulation disorder most commonly found in Ashkenazi and Iraqi Jews, but it is also found in other ethnic groups. It is a trauma or surgery-related bleeding disorder, but spontaneous bleeding is rarely seen. The clinical manifestation of bleeding in FXI deficiency cases is variable and seems to poorly correlate with plasma FXI levels. The molecular pathology of FXI deficiency is mutation in the F11 gene on the chromosome band 4q35. We report a novel mutation of the F11 gene in an 18-year-old asymptomatic Korean woman with mild FXI deficiency. Pre-operative laboratory screen tests for lipoma on her back revealed slightly prolonged activated partial thromboplastin time (45.2 sec; reference range, 23.2-39.4 sec). Her FXI activity (35%) was slightly lower than the normal FXI activity (reference range, 50-150%). Direct sequence analysis of the F11 gene revealed a heterozygous A to G substitution in nucleotide 1517 ( c.1517A>G ) of exon 13, resulting in the substitution of aspartic acid with glycine in codon 506 ( p.Asp506Gly ). To the best of our knowledge, the Asp506Gly is a novel missense mutation, and this is the first genetically confirmed case of mild FXI deficiency in Korea.
22016685	[]	[]
21850008	[ "Mutations", "in", "mitochondrially", "encoded", "complex", "I", "enzyme", "as", "the", "second", "common", "cause", "in", "a", "cohort", "of", "Chinese", "patients", "with", "mitochondrial", "myopathy,", "encephalopathy,", "lactic", "acidosis", "and", "stroke-like"...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Mutations in mitochondrially encoded complex I enzyme as the second common cause in a cohort of Chinese patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes.
21850008	[ "The", "mutation", "pattern", "of", "mitochondrial", "DNA", "(mtDNA)", "in", "mainland", "Chinese", "patients", "with", "mitochondrial", "myopathy,", "encephalopathy,", "lactic", "acidosis", "and", "stroke-like", "episodes", "(MELAS)", "has", "been", "rarely", "report...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	The mutation pattern of mitochondrial DNA (mtDNA) in mainland Chinese patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) has been rarely reported, though previous data suggested that the mutation pattern of MELAS could be different among geographically localized populations. We presented the results of comprehensive mtDNA mutation analysis in 92 unrelated Chinese patients with MELAS (85 with classic MELAS and 7 with MELAS/Leigh syndrome (LS) overlap syndrome). The mtDNA A3243G mutation was the most common causal genotype in this patient group (79/92 and 85.9%). The second common gene mutation was G13513A (7/92 and 7.6%). Additionally, we identified T10191C ( p.S45P ) in ND3, A11470C ( p. K237N ) in ND4, T13046C ( p.M237T ) in ND5 and a large-scale deletion (13025-13033:14417-14425) involving partial ND5 and ND6 subunits of complex I in one patient each. Among them, A11470C , T13046C and the single deletion were novel mutations. In summary, patients with mutations affecting mitochondrially encoded complex I (MTND) reached 12.0% (11/92) in this group. It is noteworthy that all seven patients with MELAS/LS overlap syndrome were associated with MTND mutations. Our data emphasize the important role of MTND mutations in the pathogenicity of MELAS, especially MELAS/LS overlap syndrome.
21850008	[]	[]
22104738	[ "Novel", "compound", "heterozygous", "mutation", "of", "MLYCD", "in", "a", "Chinese", "patient", "with", "malonic", "aciduria." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Novel compound heterozygous mutation of MLYCD in a Chinese patient with malonic aciduria.
22104738	[ "A", "3-year-old", "Chinese", "boy", "presented", "with", "prominent", "clinical", "features", "of", "malonic", "aciduria,", "including", "developmental", "delay,", "short", "stature,", "brain", "abnormalities", "and", "massive", "excretion", "of", "malonic", "acid", ...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	A 3-year-old Chinese boy presented with prominent clinical features of malonic aciduria, including developmental delay, short stature, brain abnormalities and massive excretion of malonic acid and methylmalonic acid. Molecular characterization by DNA sequencing analysis and multiplex ligation-dependent probe amplification of the MLYCD gene revealed a heterozygous mutation ( c.920T>G , p.Leu307Arg ) in the patient and his father and a heterozygous deletion comprising exon 1 in the patient and his mother. The missense mutation ( c.920T>G ) was not found in 100 healthy controls and has not been reported previously. Our findings expand the number of reported cases and add a novel entry to the repertoire of MLYCD mutations.
22104738	[]	[]
22295085	[ "Genetic", "and", "epigenetic", "alterations", "of", "the", "NF2", "gene", "in", "sporadic", "vestibular", "schwannomas." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Genetic and epigenetic alterations of the NF2 gene in sporadic vestibular schwannomas.
22295085	[ "BACKGROUND:", "Mutations", "in", "the", "neurofibromatosis", "type", "2", "(NF2)", "tumor-suppressor", "gene", "have", "been", "identified", "in", "not", "only", "NF2-related", "tumors", "but", "also", "sporadic", "vestibular", "schwannomas", "(VS).", "This", "stud...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	BACKGROUND: Mutations in the neurofibromatosis type 2 (NF2) tumor-suppressor gene have been identified in not only NF2-related tumors but also sporadic vestibular schwannomas (VS). This study investigated the genetic and epigenetic alterations in tumors and blood from 30 Korean patients with sporadic VS and correlated these alterations with tumor behavior. METHODOLOGY/PRINCIPAL FINDINGS: NF2 gene mutations were detected using PCR and direct DNA sequencing and three highly polymorphic microsatellite DNA markers were used to assess the loss of heterozygosity (LOH) from chromosome 22. Aberrant hypermethylation of the CpG island of the NF2 gene was also analyzed. The tumor size, the clinical growth index, and the proliferative activity assessed using the Ki-67 labeling index were evaluated. We found 18 mutations in 16 cases of 30 schwannomas (53%). The mutations included eight frameshift mutations, seven nonsense mutations, one in-frame deletion, one splicing donor site, and one missense mutation. Nine patients (30%) showed allelic loss. No patient had aberrant hypermethylation of the NF2 gene and correlation between NF2 genetic alterations and tumor behavior was not observed in this study. CONCLUSIONS/SIGNIFICANCE: The molecular genetic changes in sporadic VS identified here included mutations and allelic loss, but no aberrant hypermethylation of the NF2 gene was detected. In addition, no clear genotype/phenotype correlation was identified. Therefore, it is likely that other factors contribute to tumor formation and growth.
22295085	[]	[]
22174939	[ "RET", "mutational", "spectrum", "in", "Hirschsprung", "disease:", "evaluation", "of", "601", "Chinese", "patients." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients.
22174939	[ "Rare", "(RVs)", "and", "common", "variants", "of", "the", "RET", "gene", "contribute", "to", "Hirschsprung", "disease", "(HSCR;", "congenital", "aganglionosis).", "While", "RET", "common", "variants", "are", "strongly", "associated", "with", "the", "commonest", "...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	Rare (RVs) and common variants of the RET gene contribute to Hirschsprung disease (HSCR; congenital aganglionosis). While RET common variants are strongly associated with the commonest manifestation of the disease (males; short-segment aganglionosis; sporadic), rare coding sequence (CDS) variants are more frequently found in the lesser common and more severe forms of the disease (females; long/total colonic aganglionosis; familial).Here we present the screening for RVs in the RET CDS and intron/exon boundaries of 601 Chinese HSCR patients, the largest number of patients ever reported. We identified 61 different heterozygous RVs (50 novel) distributed among 100 patients (16.64%). Those include 14 silent, 29 missense, 5 nonsense, 4 frame-shifts, and one in-frame amino-acid deletion in the CDS, two splice-site deletions, 4 nucleotide substitutions and a 22-bp deletion in the intron/exon boundaries and 1 single-nucleotide substitution in the 5' untranslated region. Exonic variants were mainly clustered in RET the extracellular domain. RET RVs were more frequent among patients with the most severe phenotype (24% vs. 15% in short-HSCR). Phasing RVs with the RET HSCR-associated haplotype suggests that RVs do not underlie the undisputable association of RET common variants with HSCR. None of the variants were found in 250 Chinese controls.
22174939	[]	[]
21943124	[ "A", "deletion", "of", "FGFR2", "creating", "a", "chimeric", "IIIb/IIIc", "exon", "in", "a", "child", "with", "Apert", "syndrome." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	A deletion of FGFR2 creating a chimeric IIIb/IIIc exon in a child with Apert syndrome.
21943124	[ "BACKGROUND:", "Signalling", "by", "fibroblast", "growth", "factor", "receptor", "type", "2", "(FGFR2)", "normally", "involves", "a", "tissue-specific", "alternative", "splice", "choice", "between", "two", "exons", "(IIIb", "and", "IIIc),", "which", "generates", "tw...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	BACKGROUND: Signalling by fibroblast growth factor receptor type 2 (FGFR2) normally involves a tissue-specific alternative splice choice between two exons (IIIb and IIIc), which generates two receptor isoforms (FGFR2b and FGFR2c respectively) with differing repertoires of FGF-binding specificity. Here we describe a unique chimeric IIIb/c exon in a patient with Apert syndrome, generated by a non-allelic homologous recombination event. CASE PRESENTATION: We present a child with Apert syndrome in whom routine genetic testing had excluded the FGFR2 missense mutations commonly associated with this disorder. The patient was found to harbour a heterozygous 1372 bp deletion between FGFR2 exons IIIb and IIIc, apparently originating from recombination between 13 bp of identical DNA sequence present in both exons. The rearrangement was not present in the unaffected parents. CONCLUSIONS: Based on the known pathogenesis of Apert syndrome, the chimeric FGFR2 protein is predicted to act in a dominant gain-of-function manner. This is likely to result from its expression in mesenchymal tissues, where retention of most of the residues essential for FGFR2b binding activity would result in autocrine activation. This report adds to the repertoire of rare cases of Apert syndrome for which a pathogenesis based on atypical FGFR2 rearrangements can be demonstrated.
21943124	[]	[]
21779184	[ "Detection", "of", "a-thalassemia-1", "Southeast", "Asian", "and", "Thai", "type", "deletions", "and", "b-thalassemia", "3.5-kb", "deletion", "by", "single-tube", "multiplex", "real-time", "PCR", "with", "SYBR", "Green1", "and", "high-resolution", "melting", "analysis...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Detection of a-thalassemia-1 Southeast Asian and Thai type deletions and b-thalassemia 3.5-kb deletion by single-tube multiplex real-time PCR with SYBR Green1 and high-resolution melting analysis.
21779184	[ "BACKGROUND:", "Prevention", "and", "control", "of", "thalassemia", "requires", "simple,", "rapid,", "and", "accurate", "screening", "tests", "for", "carrier", "couples", "who", "are", "at", "risk", "of", "conceiving", "fetuses", "with", "severe", "thalassemia.", ...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	BACKGROUND: Prevention and control of thalassemia requires simple, rapid, and accurate screening tests for carrier couples who are at risk of conceiving fetuses with severe thalassemia. METHODS: Single-tube multiplex real-time PCR with SYBR Green1 and high-resolution melting (HRM) analysis were used for the identification of a-thalassemia-1 Southeast Asian (SEA) and Thai type deletions and b-thalassemia 3.5-kb gene deletion. The results were compared with those obtained using conventional gap-PCR. DNA samples were derived from 28 normal individuals, 11 individuals with a-thalassemia-1 SEA type deletion, 2 with a-thalassemia-1 Thai type deletion, and 2 with heterozygous b-thalassemia 3.5-kb gene deletion. RESULTS: HRM analysis indicated that the amplified fragments from a-thalassemia-1 SEA type deletion, a-thalassemia-1 Thai type deletion, b-thalassemia 3.5-kb gene deletion, and the wild-type b-globin gene had specific peak heights at mean melting temperature (T(m)) values of 86.89 , 85.66 , 77.24 , and 74.92 , respectively. The results obtained using single-tube multiplex real-time PCR with SYBR Green1 and HRM analysis showed 100% consistency with those obtained using conventional gap-PCR. CONCLUSIONS: Single-tube multiplex real-time PCR with SYBR Green1 and HRM analysis is a potential alternative for routine clinical screening of the common types of a- and b-thalassemia large gene deletions, since it is simple, cost-effective, and highly accurate.
21779184	[]	[]
21640722	[ "Xeroderma", "pigmentosum", "variant:", "complementary", "molecular", "approaches", "to", "detect", "a", "13", "base", "pair", "deletion", "in", "the", "DNA", "polymerase", "eta", "gene." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Xeroderma pigmentosum variant: complementary molecular approaches to detect a 13 base pair deletion in the DNA polymerase eta gene.
21640722	[ "Deficiencies", "of", "DNA", "polymerase", "eta-an", "enzyme", "mediating", "replication", "past", "UV-induced", "DNA", "damage-predispose", "individuals", "to", "xeroderma", "pigmentosum", "variant", "(XPV)", "and", "result", "in", "a", "high", "incidence", "of", "...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	Deficiencies of DNA polymerase eta-an enzyme mediating replication past UV-induced DNA damage-predispose individuals to xeroderma pigmentosum variant (XPV) and result in a high incidence of skin cancers. We designed, developed and assessed several complementary molecular approaches to detect a genetically inherited deletion within DNA polymerase eta. RNA was reverse transcribed from XPV fibroblasts and from normal human cells, and standard polymerase chain reaction (PCR) was conducted on the cDNA targeting a region with a 13 base pair deletion within the polymerase eta gene. PCR products were subjected to restriction fragment length polymorphism (RFLP) analysis and cycle DNA sequencing. The deletion was found to eliminate a BsrGI restriction site and affected the number of resultant fragments visualized after gel electrophoresis. Cycle sequencing of polymerase eta-specific amplicons from XPV and normal cells provided a second approach for detecting the mutation. Additionally, the use of a fluorescent nucleic acid dye-EvaGreen-in real-time PCR and melt curve analysis distinguished normal and XPV patient-derived amplicons as well as heteroduplexes that represent heterozygotic carriers without the need for high resolution melt analysis-compatible software. Our approaches are easily adaptable by diagnostic laboratories that screen for or verify genetically inherited disorders and identify carriers of a defective gene.
21640722	[]	[]
21499297	[ "C10ORF97", "is", "a", "novel", "tumor-suppressor", "gene", "of", "non-small-cell", "lung", "cancer", "and", "a", "functional", "variant", "of", "this", "gene", "increases", "the", "risk", "of", "non-small-cell", "lung", "cancer." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	C10ORF97 is a novel tumor-suppressor gene of non-small-cell lung cancer and a functional variant of this gene increases the risk of non-small-cell lung cancer.
21499297	[ "In", "an", "earlier", "study", "we", "showed", "that", "C10ORF97", "(chromosome-10,", "open", "reading", "frame-97)", "was", "expressed", "in", "almost", "all", "of", "the", "tissues", "and", "cell", "lines", "tested,", "and", "that", "it", "inhibited", "the"...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	In an earlier study we showed that C10ORF97 (chromosome-10, open reading frame-97) was expressed in almost all of the tissues and cell lines tested, and that it inhibited the growth of seven tumor cell lines, including two lung carcinoma cell lines (A549 and PG). Here, we show that C10ORF97 is downregulated in non-small-cell lung cancer (NSCLC) tissue compared with normal lung tissue. Overexpression of C10ORF97 significantly suppressed human lung carcinoma A549 cell growth (proliferation and anchorage-independent growth in soft agar) and motility (migration and adhesion). This tumor-suppressive function of C10ORF97 was also verified in vivo. We further found that C10ORF97 caused G(1) arrest of A549 cells and modulated the expression level of several cell-cycle regulators (such as CDK2, cyclin-E and p27). These effects of C10ORF97 were mediated by physical association between C10ORF97 and Jun-activating domain-binding protein-1 (JAB1), and blocking of JAB1-mediated translocation of p27 from the nucleus to the cytoplasm. Together, these results indicated that C10ORF97 functions as a novel tumor suppressor by modulating several key G(1)/S-regulatory proteins by interacting with JAB1. These findings led us to hypothesize that a single-nucleotide polymorphism (SNP) in the C10ORF97 gene that affects its expression might be associated with susceptibility to NSCLC. SNP216 C>T ( rs2297882 ) in the C10ORF97 Kozak sequence was identified, and allele T of SNP216 suppressed C10ORF97 expression in vitro and in vivo. Furthermore, the TT genotype of SNP216 was associated with an increased risk of NSCLC (adjusted odds ratio=1.73 (95% confidence interval: 1.33-2.25), P=4.6 10(-5)). These data indicated that C10ORF97 is a tumor suppressor of NSCLC progression and C10ORF97-SNP216 may serve as a predictor of NSCLC.
21499297	[]	[]
21695597	[ "MHC", "region", "and", "risk", "of", "systemic", "lupus", "erythematosus", "in", "African", "American", "women." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	MHC region and risk of systemic lupus erythematosus in African American women.
21695597	[ "The", "major", "histocompatibility", "complex", "(MHC)", "on", "chromosome", "6p21", "is", "a", "key", "contributor", "to", "the", "genetic", "basis", "of", "systemic", "lupus", "erythematosus", "(SLE).", "Although", "SLE", "affects", "African", "Americans", "dis...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	The major histocompatibility complex (MHC) on chromosome 6p21 is a key contributor to the genetic basis of systemic lupus erythematosus (SLE). Although SLE affects African Americans disproportionately compared to European Americans, there has been no comprehensive analysis of the MHC region in relationship to SLE in African Americans. We conducted a screening of the MHC region for 1,536 single nucleotide polymorphisms (SNPs) and the deletion of the C4A gene in a SLE case-control study (380 cases, 765 age-matched controls) nested within the prospective Black Women's Health Study. We also genotyped 1,509 ancestral informative markers throughout the genome to estimate European ancestry to control for population stratification due to population admixture. The most strongly associated SNP with SLE was the rs9271366 (odds ratio, OR = 1.70, p = 5.6 10(-5)) near the HLA-DRB1 gene. Conditional haplotype analysis revealed three other SNPs, rs204890 (OR = 1.86, p = 1.2 10(-4)), rs2071349 (OR = 1.53, p = 1.0 10(-3)), and rs2844580 (OR = 1.43, p = 1.3 10(-3)), to be associated with SLE independent of the rs9271366 SNP. In univariate analysis, the OR for the C4A deletion was 1.38, p = 0.075, but after simultaneous adjustment for the other four SNPs the odds ratio was 1.01, p = 0.98. A genotype score combining the four newly identified SNPs showed an additive risk according to the number of high-risk alleles (OR = 1.67 per high-risk allele, p < 0.0001). Our strongest signal, the rs9271366 SNP, was also associated with higher risk of SLE in a previous Chinese genome-wide association study (GWAS). In addition, two SNPs found in a GWAS of European ancestry women were confirmed in our study, indicating that African Americans share some genetic risk factors for SLE with European and Chinese subjects. In summary, we found four independent signals in the MHC region associated with risk of SLE in African American women.
21695597	[]	[]
21629979	[ "Molecular", "and", "clinical", "analysis", "of", "glioblastoma", "with", "an", "oligodendroglial", "component", "(GBMO)." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Molecular and clinical analysis of glioblastoma with an oligodendroglial component (GBMO).
21629979	[ "The", "genetic", "and", "clinical", "features", "of", "glioblastoma", "with", "an", "oligodendroglial", "component", "(GBMO),", "pathologically", "defined", "as", "anaplastic", "oligo-astrocytoma", "with", "necrosis,", "remain", "unclear.", "We", "investigated", "the",...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	The genetic and clinical features of glioblastoma with an oligodendroglial component (GBMO), pathologically defined as anaplastic oligo-astrocytoma with necrosis, remain unclear. We investigated the correlation between genetic alterations and clinical outcomes in 19 GBMO patients we have encountered since 1997. Using single nucleotide polymorphism oligonucleotide genomic (SNP) microarrays, we analyzed gene amplification, loss of heterozygosity (LOH), and homozygous deletions in their whole genome. We also analyzed their overall survival (OS). Pathological studies revealed the presence of calcification in 11 and of a cyst in 9 of the 19 patients. Whole-genome analysis using SNP microarrays revealed LOH of chromosome 10 in 11, EGFR amplification in 8, 9p21 (INK4 locus) deletion in 12, PDGFR amplification in 2, and LOH of 1p19q in 2 patients. Median OS was 14 months (average 22.8 months). The pattern of genetic alterations was similar in GBMO and glioblastoma multiforme (GBM) patients, and the clinical outcomes were similar in GBMO and GBM patients.
21629979	[]	[]
22048266	[ "Exploratory", "investigation", "on", "functional", "significance", "of", "ETS2", "and", "SIM2", "genes", "in", "Down", "syndrome." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Exploratory investigation on functional significance of ETS2 and SIM2 genes in Down syndrome.
22048266	[ "Trisomy", "of", "the", "21{st}", "chromosome", "leads", "to", "an", "over", "dosage", "of", "several", "regulatory", "genes", "in", "Down", "syndrome", "(DS).", "Though", "allelic", "and", "genotypic", "combinations", "formed", "between", "genes", "are", "inter...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	Trisomy of the 21{st} chromosome leads to an over dosage of several regulatory genes in Down syndrome (DS). Though allelic and genotypic combinations formed between genes are interesting, till date, this particular area has never been explored in DS. In the present investigation four SNPs in two transcription factors, Single minded 2 (SIM2) and V-ets erythroblastosis virus E26 oncogene homolog2 (ETS2), located in the 21{st} chromosome were genotyped to understand their role in DS. Genomic DNA of eastern Indian probands with DS (N=132), their parents (N=209) and ethnically matched controls (N=149) was subjected to PCR-based analyses of functionally important SNPs followed by statistical analyses. ETS2 rs461155 showed high heterozygosity in DS. Significantly lower frequency of SIM2 C-G haplotype ( rs2073601 - rs2073416 ) was noticed in individuals with DS (P value =0.01669) and their fathers (P value=0.01185). Significantly lower frequency of the A-C-C-G with higher frequency of A-C-A-G haplotypes was also noticed in subjects with DS (P value =0.02089 and 0.00588 respectively). Data obtained indicate that the rs2073601 'A' allele, responsible for nonsynonymous substitution of leucine to methionine, may have some role in DS in this population.
22048266	[]	[]
22028770	[ "APOE", "genotype-function", "relationship:", "evidence", "of", "-491", "A/T", " ", "promoter", "polymorphism", "modifying", "transcription", "control", "but", "not", "type", "2", "diabetes", "risk." ]	[ 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	APOE genotype-function relationship: evidence of -491 A/T promoter polymorphism modifying transcription control but not type 2 diabetes risk.
22028770	[ "BACKGROUND:", "The", "apolipoprotein", "E", "gene", "(APOE)", "coding", "polymorphism", "modifies", "the", "risks", "of", "Alzheimer's", "disease,", "type", "2", "diabetes,", "and", "coronary", "heart", "disease.", "Aside", "from", "the", "coding", "variants,", "...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	BACKGROUND: The apolipoprotein E gene (APOE) coding polymorphism modifies the risks of Alzheimer's disease, type 2 diabetes, and coronary heart disease. Aside from the coding variants, single nucleotide polymorphism (SNP) of the APOE promoter has also been shown to modify the risk of Alzheimer's disease. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigate the genotype-function relationship of APOE promoter polymorphism at molecular level and at physiological level: i.e., in transcription control of the gene and in the risk of type 2 diabetes. In molecular studies, the effect of the APOE -491A/T ( rs449647 ) polymorphism on gene transcription was accessed by dual-luciferase reporter gene assays. The -491 A to T substitution decreased the activity (p<0.05) of the cloned APOE promoter (-1017 to +406). Using the -501 to -481 nucleotide sequence of the APOE promoter as a 'bait' to screen the human brain cDNA library by yeast one-hybrid system yielded ATF4, an endoplasmic reticulum stress response gene, as one of the interacting factors. Electrophoretic-mobility-shift assays (EMSA) and chromatin immuno-precipitation (ChIP) analyses further substantiated the physical interaction between ATF4 and the APOE promoter. Over-expression of ATF4 stimulated APOE expression whereas siRNA against ATF4 suppressed the expression of the gene. However, interaction between APOE promoter and ATF4 was not -491A/T -specific. At physiological level, the genotype-function relationship of APOE promoter polymorphism was studied in type 2 diabetes. In 630 cases and 595 controls, three APOE promoter SNPs -491A/T , -219G/T ( rs405509 ), and +113G/C ( rs440446 ) were genotyped and tested for association with type 2 diabetes in Hong Kong Chinese. No SNP or haplotype association with type 2 diabetes was detected. CONCLUSIONS/SIGNIFICANCE: At molecular level, polymorphism -491A/T and ATF4 elicit independent control of APOE gene expression. At physiological level, no genotype-risk association was detected between the studied APOE promoter SNPs and type 2 diabetes in Hong Kong Chinese.
22028770	[]	[]
21771880	[ "Resequencing", "of", "IRS2", "reveals", "rare", "variants", "for", "obesity", "but", "not", "fasting", "glucose", "homeostasis", "in", "Hispanic", "children." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Resequencing of IRS2 reveals rare variants for obesity but not fasting glucose homeostasis in Hispanic children.
21771880	[ "Our", "objective", "was", "to", "resequence", "insulin", "receptor", "substrate", "2", "(IRS2)", "to", "identify", "variants", "associated", "with", "obesity-", "and", "diabetes-related", "traits", "in", "Hispanic", "children.", "Exonic", "and", "intronic", "segmen...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	Our objective was to resequence insulin receptor substrate 2 (IRS2) to identify variants associated with obesity- and diabetes-related traits in Hispanic children. Exonic and intronic segments, 5' and 3' flanking regions of IRS2 ( 14.5 kb), were bidirectionally sequenced for single nucleotide polymorphism (SNP) discovery in 934 Hispanic children using 3730XL DNA Sequencers. Additionally, 15 SNPs derived from Illumina HumanOmni1-Quad BeadChips were analyzed. Measured genotype analysis tested associations between SNPs and obesity and diabetes-related traits. Bayesian quantitative trait nucleotide analysis was used to statistically infer the most likely functional polymorphisms. A total of 140 SNPs were identified with minor allele frequencies (MAF) ranging from 0.001 to 0.47. Forty-two of the 70 coding SNPs result in nonsynonymous amino acid substitutions relative to the consensus sequence; 28 SNPs were detected in the promoter, 12 in introns, 28 in the 3'-UTR, and 2 in the 5'-UTR. Two insertion/deletions (indels) were detected. Ten independent rare SNPs (MAF = 0.001-0.009) were associated with obesity-related traits (P = 0.01-0.00002). SNP 10510452_139 in the promoter region was shown to have a high posterior probability (P = 0.77-0.86) of influencing BMI, fat mass, and waist circumference in Hispanic children. SNP 10510452_139 contributed between 2 and 4% of the population variance in body weight and composition. None of the SNPs or indels were associated with diabetes-related traits or accounted for a previously identified quantitative trait locus on chromosome 13 for fasting serum glucose. Rare but not common IRS2 variants may play a role in the regulation of body weight but not an essential role in fasting glucose homeostasis in Hispanic children.
21771880	[]	[]
21790735	[ "A", "large", "heterozygous", "deletion", "including", "the", "entire", "C1", "inhibitor", "gene", "in", "a", "sporadic", "case", "of", "hereditary", "angio-oedema." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	A large heterozygous deletion including the entire C1 inhibitor gene in a sporadic case of hereditary angio-oedema.
21790735	[ "C1", "inhibitor", "(C1-INH)", "deficiency", "[hereditary", "or", "acquired", "angio-oedema", "(HAE", "or", "AAE)]", "is", "characterized", "by", "recurring", "episodes", "of", "subcutaneous", "or", "submucosal", "oedema.", "Many", "different", "mutations", "in", "t...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	C1 inhibitor (C1-INH) deficiency [hereditary or acquired angio-oedema (HAE or AAE)] is characterized by recurring episodes of subcutaneous or submucosal oedema. Many different mutations in the C1-INH gene have been identified as a cause of HAE. We investigated the molecular basis of the disease in a Japanese woman with sporadic HAE. Direct sequencing of genomic DNA revealed no point mutation in the C1-INH gene. Quantitative real-time PCR showed that the copy number of the C1-INH gene in the patient was half that of a healthy control. Furthermore, we identified a 650-kbp deletion on the chromosome, which included the C1-INH gene. We evaluated the correlation between the patient's attacks and her coagulation activity. The levels of D-dimer were high during the angio-oedema attacks, and often exceeded the normal range even during remission, thus the level of D-dimer reflected the activity of HAE in this patient.
21790735	[]	[]
21506149	[ "Phenotype", "of", "the", "202", "adenine", "deletion", "in", "the", "parkin", "gene:", "40", "years", "of", "follow-up." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Phenotype of the 202 adenine deletion in the parkin gene: 40 years of follow-up.
21506149	[ "BACKGROUND:", "We", "describe", "the", "four", "decades", "follow-up", "of", "14", "parkin", "patients", "belonging", "to", "two", "large", "eight-generation-long", "in-bred", "Muslim-Arab", "kindreds.", "RESULTS:", "All", "patients", "had", "a", "single", "base-pa...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	BACKGROUND: We describe the four decades follow-up of 14 parkin patients belonging to two large eight-generation-long in-bred Muslim-Arab kindreds. RESULTS: All patients had a single base-pair of adenine deletion at nucleotide 202 of exon 2 (202A) of the parkin gene (all homozygous, one heterozygous). Parkinson's disease onset age was 17-68 years. Special features were intractable axial symptoms (low back pain, scoliosis, camptocormia, antecollis), postural tremor, and preserved cognition. CONCLUSIONS: The 202A deletion of the parkin gene causes early-onset Parkinson's disease with marked levodopa/STN-DBS-resistant axial features. Postural tremor and preserved cognition, even after 40 years of disease, were also evident.
21506149	[]	[]
21904390	[ "Two", "novel", "mutations", "of", "the", "PAX6", "gene", "causing", "different", "phenotype", "in", "a", "cohort", "of", "Chinese", "patients." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Two novel mutations of the PAX6 gene causing different phenotype in a cohort of Chinese patients.
21904390	[ "PURPOSE:", "Aniridia", "(AN)", "is", "a", "rare", "congenital", "panocular", "disorder", "caused", "by", "the", "mutations", "of", "the", "paired", "box", "homeotic", "gene", "6(PAX6)", "gene.", "The", "PAX6gene", "is", "also", "involved", "in", "other", "ant...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	PURPOSE: Aniridia (AN) is a rare congenital panocular disorder caused by the mutations of the paired box homeotic gene 6(PAX6) gene. The PAX6gene is also involved in other anterior segment malformations including Peters anomaly. We studied the PAX6gene mutations in a cohort of affected individuals with different clinical phenotype including AN, coloboma of iris and choroid, or anterior segment malformations. PATIENTS AND METHODS: Six unrelated families and 10 sporadic patients were examined clinically. After informed consent was obtained, genomic DNA was extracted from the venous blood of all participants. Mutation screening of all exons of the PAX6gene was performed by direct sequencing of PCR-amplified DNA fragments. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect large deletions. RESULTS: By clinical examination, the patients and the pedigrees were divided into the following three groups: AN, coloboma of iris and choroids, and the anterior segment malformations including peters anomaly. Sequencing of the PAX6gene, three intragenic mutations including a novel heterozygous splicing-site mutations c.357-3C>G ( p.Ser119fsX ) were identified in the patients of the AN group. A novel missense mutation c.643T>C ( p.S216P ) was detected in the anterior segment malformation group. The mutation p.S216P located in the homeodomain region of the PAX6 caused the phenotype of Peters anomaly in family A6 with different expressing. Through MLPA analysis, a large deletion including the whole PAX6gene and DKFZ p686k1684gene was detected in one sporadic patient from the AN group. Neither intragenic mutation nor large deletion was identified in the group with coloboma of iris and choroid. CONCLUSION: Our findings further confirmed that different kind of mutations might cause different ocular phenotype, and clearly clinical phenotype classification might increase the mutation detection rate of the PAX6gene.
21904390	[]	[]
21496008	[ "Screening", "and", "cell-based", "assessment", "of", "mutations", "in", "the", "Aristaless-related", "homeobox", "(ARX)", "gene." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Screening and cell-based assessment of mutations in the Aristaless-related homeobox (ARX) gene.
21496008	[ "ARX", "mutations", "cause", "a", "diverse", "spectrum", "of", "human", "disorders,", "ranging", "from", "severe", "brain", "and", "genital", "malformations", "to", "non-syndromic", "intellectual", "disability", "(ID).", "ARX", "is", "a", "transcription", "factor", ...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1...	ARX mutations cause a diverse spectrum of human disorders, ranging from severe brain and genital malformations to non-syndromic intellectual disability (ID). ARX is a transcription factor with multiple domains that include four polyalanine (pA) tracts, the first two of which are frequently expanded by mutations. We progressively screened DNA samples from 613 individuals with ID initially for the most frequent ARX mutations ( c.304ins(GCG) (7)'expansion' of pA1 and c.429_452dup ' dup24bp ' of pA2). Five hundred samples without pA1 or pA2 mutations had the entire ARX ORF screened by single stranded polymorphism conformation (SSCP) and/or denaturing high pressure liquid chromatography (dHPLC) analysis. Overall, eight families with six mutations in ARX were identified (1.31%): five duplication mutations in pA2 (0.82%) with three new clinical reports of families with the dup24bp and two duplications larger than the dup24bp mutation discovered ( dup27bp , dup33bp ); and three point mutations (0.6%), including one novel mutation in the homeodomain ( c.1074G>T ). Four ultraconserved regions distal to ARX (uc466-469) were also screened in a subset of 94 patients, with three unique nucleotide changes identified in two (uc466, uc467). The subcellular localization of full length ARX proteins was assessed for 11 variants. Protein mislocalization increased as a function of pA2 tract length and phenotypic severity, as has been previously suggested for pA1. Similarly, protein mislocalization of the homeodomain mutations also correlated with clinical severity, suggesting an emerging genotype vs cellular phenotype correlation.
21496008	[]	[]
21717135	[ "Variation", "in", "genotype", "and", "higher", "virulence", "of", "a", "strain", "of", "Sporothrix", "schenckii", "causing", "disseminated", "cutaneous", "sporotrichosis." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Variation in genotype and higher virulence of a strain of Sporothrix schenckii causing disseminated cutaneous sporotrichosis.
21717135	[ "Sporotrichosis", "is", "usually", "a", "localized,", "lymphocutaneous", "disease,", "but", "its", "disseminated", "type", "was", "rarely", "reported.", "The", "main", "objective", "of", "this", "study", "was", "to", "identify", "specific", "DNA", "sequence", "var...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	Sporotrichosis is usually a localized, lymphocutaneous disease, but its disseminated type was rarely reported. The main objective of this study was to identify specific DNA sequence variation and virulence of a strain of Sporothrix schenckii isolated from the lesion of disseminated cutaneous sporotrichosis. We confirmed this strain to be S. schenckii by( ) tubulin and chitin synthase gene sequence analysis in addition to the routine mycological and partial ITS and NTS sequencing. We found a 10-bp deletion in the ribosomal NTS region of this strain, in reference to the sequence of control strains isolated from fixed cutaneous sporotrichosis. After inoculated into immunosuppressed mice, this strain caused more extensive system involvement and showed stronger virulence than the control strain isolated from a fixed cutaneous sporotrichosis. Our study thus suggests that different clinical manifestation of sporotrichosis may be associated with variation in genotype and virulence of the strain, independent of effects due to the immune status of the host.
21717135	[]	[]
21976953	[ "Identification", "of", "a", "novel", "FBN1", "gene", "mutation", "in", "a", "Chinese", "family", "with", "Marfan", "syndrome." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Identification of a novel FBN1 gene mutation in a Chinese family with Marfan syndrome.
21976953	[ "PURPOSE:", "To", "identify", "the", "mutation", "in", "the", "fibrillin-1", "gene", "(FBN1)", "in", "a", "Chinese", "family", "with", "Marfan", "syndrome", "(MFS).", "METHODS:", "Patients", "and", "family", "members", "were", "given", "complete", "physical,", "...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	PURPOSE: To identify the mutation in the fibrillin-1 gene (FBN1) in a Chinese family with Marfan syndrome (MFS). METHODS: Patients and family members were given complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA was extracted from leukocytes of venous blood of six individuals in the family and 170 healthy Chinese individuals. All of the 65 coding exons and their flanking intronic boundaries of FBN1 were amplified in the proband by polymerase chain reaction and followed by direct sequencing. The mutation identified in the proband was screened in the other family members and the 170 healthy Chinese individuals by direct sequencing. Protein conservation analysis was performed in six species using an online ClustalW tool. Protein structure was modeled based on the Protein data bank and mutated in DeepView v4.0.1 to predict the functional consequences of the mutation. RESULTS: A novel heterozygous c.3703T>C change in exon 29 of FBN1 was detected in the proband, which resulted in the substitution of serine by proline at codon 1235 ( p.S1235P ). This mutation was also present in two family members but absent in the other, unaffected family members and the 170 healthy Chinese individuals. The mutant residue located in the calcium binding epidermal growth factor-like#15 domain is highly conserved among mammalian species and could probably induce conformation change of the domain. CONCLUSIONS: We indentified a novel p.S1235P mutation in FBN1, which is the causative mutation for MFS in this family. Our result expands the mutation spectrum of FBN1 and contributes to the study of the molecular pathogenesis of Marfan syndrome.
21976953	[]	[]
21546516	[ "The", "57", "kb", "deletion", "in", "cystinosis", "patients", "extends", "into", "TRPV1", "causing", "dysregulation", "of", "transcription", "in", "peripheral", "blood", "mononuclear", "cells." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	The 57 kb deletion in cystinosis patients extends into TRPV1 causing dysregulation of transcription in peripheral blood mononuclear cells.
21546516	[ "BACKGROUND:", "Cystinosis", "is", "an", "autosomal", "recessive", "disease", "characterised", "by", "the", "abnormal", "accumulation", "of", "lysosomal", "cystine.", "Mutations", "in", "the", "cystinosin", "gene", "(CTNS)", "represent", "known", "causes", "for", "t...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	BACKGROUND: Cystinosis is an autosomal recessive disease characterised by the abnormal accumulation of lysosomal cystine. Mutations in the cystinosin gene (CTNS) represent known causes for the disease. The major cystinosis mutation is a 57 kb deletion on human chromosome 17p13 that removes the majority of CTNS and the entire adjacent gene, CARKL/SHPK. OBJECTIVES: In order to identify other genes that may influence the cystinosis pathobiological pathway, peripheral blood mononuclear cells (PBMC) were collected from cystinosis family members, and DNA and RNA extracted. RESULTS: Using whole genome transcriptional profiling, transient receptor potential vanilloid 1 (TRPV1) was found to be differentially expressed in association with cystinosis. This was verified using TaqMan qRT-PCR. There was a 72% reduction in PBMC TRPV1 mRNA levels in cystinosis individuals homozygous for the 57 kb deletion (n=6) compared to unaffected individuals without the deletion (n=6) (p=0.002). TRPV1 is a sensory receptor located on chromosome 17p13, adjacent to CARKL/SHPK. It was ascertained that the 57 kb deletion extends from exon 10 of CTNS, upstream through CARKL/SHPK, to intron 2 of TRPV1, thus deleting the first two non-coding exons. CONCLUSION: This is the first study to report that the 57 kb deletion extends into the TRPV1 gene causing dysregulation of transcription in PBMC isolated from cystinosis patients.
21546516	[]	[]
21799811	[ "Strong", "association", "of", "677", "C>T", " ", "substitution", "in", "the", "MTHFR", "gene", "with", "male", "infertility--a", "study", "on", "an", "indian", "population", "and", "a", "meta-analysis." ]	[ 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Strong association of 677 C>T substitution in the MTHFR gene with male infertility--a study on an indian population and a meta-analysis.
21799811	[ "BACKGROUND:", "Methylenetetrahydrofolate", "reductase", "(MTHFR)", "is", "an", "important", "enzyme", "of", "folate", "and", "methionine", "metabolism,", "making", "it", "crucial", "for", "DNA", "synthesis", "and", "methylation.", "The", "objective", "of", "this", ...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate and methionine metabolism, making it crucial for DNA synthesis and methylation. The objective of this study was to analyze MTHFR gene 677C>T polymorphism in infertile male individuals from North India, followed by a meta-analysis on our data and published studies. METHODOLOGY/PRINCIPAL FINDINGS: We undertook genotyping on a total of 837 individuals including well characterized infertile (N=522) and confirmed fertile (N=315) individuals. The SNP was typed by direct DNA sequencing. Chi square test was done for statistical analysis. Published studies were searched using appropriate keywords. Source of data collection for meta-analysis included 'Pubmed', 'Ovid' and 'Google Scholar'. Those studies analyzing 677C>T polymorphism in male infertility and presenting all relevant data were included in meta-analysis. The genotype data for infertile subjects and fertile controls was extracted from each study. Chi square test was done to obtain odds ratio (OR) and p-value. Meta-analysis was performed using Comprehensive Meta-analysis software (Version 2). The frequency of mutant (T) allele (p=0.0025) and genotypes (CT+TT) (p=0.0187) was significantly higher in infertile individuals in comparison to fertile controls in our case-control study. The overall summary estimate (OR) for allele and genotype meta-analysis were 1.304 (p=0.000), 1.310 (p=0.000), respectively, establishing significant association of 677C>T polymorphism with male infertility. CONCLUSIONS/SIGNIFICANCE: 677C>T substitution associated strongly with male infertility in Indian population. Allele and genotype meta-analysis also supported its strong correlation with male infertility, thus establishing it as a risk factor.
21799811	[]	[]
21976404	[ "Angiotensin-converting", "enzyme", "(ACE)", "serum", "levels", "and", "gene", "polymorphism", "in", "Egyptian", "patients", "with", "systemic", "lupus", "erythematosus." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Angiotensin-converting enzyme (ACE) serum levels and gene polymorphism in Egyptian patients with systemic lupus erythematosus.
21976404	[ "OBJECTIVES:", "To", "investigate", "the", "association", "of", "angiotensin-converting", "enzyme", "(ACE)", "gene", "polymorphism", "and", "serum", "ACE", "level", "among", "Egyptian", "SLE", "patients", "and", "its", "relation", "to", "disease", "activity", "param...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	OBJECTIVES: To investigate the association of angiotensin-converting enzyme (ACE) gene polymorphism and serum ACE level among Egyptian SLE patients and its relation to disease activity parameters. SUBJECTS AND METHODS: We enrolled 50 Egyptian female systemic lupus erythematosus (SLE) patients and 29 healthy controls. Measurement of serum ACE level was done using ELISA, and the ACE genotype was determined by polymerase chain reaction using genomic DNA from peripheral blood. RESULTS: A significant difference was found in ACE genotypes between SLE patients and controls ( (2 )= 7.84, p = 0.02). The frequency of ACE DD versus (DI and II) genotypes was significantly higher in SLE patients compared with controls ( (2 )= 5.57, p = 0.018 and OR for risk of SLE was 3.1 with 95% confidence interval: 1.198.06). Mean serum ACE level was significantly higher in the SLE group compared with controls (p = 0.006). Subjects with DD genotype had a significantly higher mean level than those with DI (p = 0.015) and II genotypes (p = 0.02). Lupus nephritis patients had a significantly higher frequency of DD versus DI and II genotypes compared with lupus patients without nephritis (Fisher's exact test, p = 0.025) and controls ( (2) =8.74, p = 0.003). SLE patients with vasculopathy had a significantly higher frequency of DD versus DI/II genotypes compared with SLE patients without vasculopathy (Fisher's exact test, p = 0.04) and controls ( (2 )= 9.84 and p = 0.002). Mean serum ACE level was significantly higher in the lupus nephritis and SLE patients with vasculopathy compared with controls (p = 0.008, p = 0.001, respectively). Significant positive correlations were found between serum ACE level and serum creatinine and 24 h proteinuria (p = 0.03, 0.009, respectively). SLE patients with DD genotype had a statistically significant higher mean SLEDAI score than those with (DI/II) genotypes (p = 0.02). Significant positive correlation was found between serum ACE levels and SLEDAI scores (p = 0.04). CONCLUSION: ACE genotype and subsequently serum ACE level could be associated with the disease activity of Egyptian SLE patients; in addition, ACE deletion polymorphism might be used as one of the predictive factors for the activity of SLE. Further studies on a larger number of patients should be done to determine the exact prevalence of ACE gene polymorphism among Egyptian SLE patients.
21976404	[]	[]
21879313	[ "Genotype", "rs8099917", " ", "near", "the", "IL28B", "gene", "and", "amino", "acid", "substitution", "at", "position", "70", "in", "the", "core", "region", "of", "the", "hepatitis", "C", "virus", "are", "determinants", "of", "serum", "apolipoprotein", "B-100"...	[ 0, 5, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Genotype rs8099917 near the IL28B gene and amino acid substitution at position 70 in the core region of the hepatitis C virus are determinants of serum apolipoprotein B-100 concentration in chronic hepatitis C.
21879313	[ "The", "life", "cycle", "of", "the", "hepatitis", "C", "virus", "(HCV)", "is", "closely", "related", "to", "host", "lipoprotein", "metabolism.", "Serum", "levels", "of", "lipid", "are", "associated", "with", "the", "response", "to", "pegylated", "interferon", ...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	The life cycle of the hepatitis C virus (HCV) is closely related to host lipoprotein metabolism. Serum levels of lipid are associated with the response to pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy, while single nucleotide polymorphisms (SNPs) around the human interleukin 28B (IL28B) gene locus and amino acid substitutions in the core region of the HCV have been reported to affect the efficacy of PEG-IFN/RBV therapy in chronic hepatitis with HCV genotype 1b infection. The aim of this study was to elucidate the relationship between serum lipid and factors that are able to predict the efficacy of PEG-IFN/RB therapy, with specific focus on apolipoprotein B-100 (apoB-100) in 148 subjects with chronic HCV G1b infection. Our results demonstrated that both the aa 70 substitution in the core region of the HCV and the rs8099917 SNP located proximal to the IL28B were independent factors in determining serum apoB-100 and low-density lipoprotein (LDL) cholesterol levels. A significant association was noted between higher levels of apoB-100 (P = 1.1 10(-3)) and LDL cholesterol (P = 0.02) and the subjects having Arg70. A significant association was also observed between subjects carrying the rs8099917 TT responder genotype and higher levels of apoB-100 (P = 6.4 10(-3)) and LDL cholesterol (P = 4.2 10(-3)). Our results suggest that apoB-100 and LDL cholesterol are markers of impaired cellular lipoprotein pathways and/or host endogenous interferon response to HCV in chronic HCV infection. In particular, serum apoB-100 concentration might be an informative marker for judging changes in HCV-associated intracellular lipoprotein metabolism in patients carrying the rs8099917 responder genotype.
21879313	[]	[]
20854438	[ "SLURP1", "mutation-impaired", "T-cell", "activation", "in", "a", "family", "with", "mal", "de", "Meleda." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	SLURP1 mutation-impaired T-cell activation in a family with mal de Meleda.
20854438	[ "BACKGROUND:", "Mal", "de", "Meleda", "(MDM)", "is", "palmoplantar", "erythrokeratoderma", "with", "an", "autosomal", "recessive", "inheritance", "and", "is", "caused", "by", "a", "mutation", "in", "the", "gene", "encoding", "SLURP-1", "(lymphocyte", "antigen", "6...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	BACKGROUND: Mal de Meleda (MDM) is palmoplantar erythrokeratoderma with an autosomal recessive inheritance and is caused by a mutation in the gene encoding SLURP-1 (lymphocyte antigen 6/urokinase-type plasminogen activator receptor related protein-1). SLURP-1 is an allosteric agonist to the nicotinic acetylcholine receptor (nAchR) and it regulates epidermal homeostasis. In addition, murine studies have shown that nAchR signalling is important for the regulation of T-cell function. Among the family members, patients with the homozygous SLURP1 (previously known as ARS component B) mutation are prone to melanoma and viral infection, which might link to defective T-cell function as well as a derangement of epidermal homeostasis. OBJECTIVES: To investigate the association of the SLURP1 gene mutation with T-cell activation in a Taiwanese family with MDM. To test that SLURP-1 is essential for T-cell activation. METHODS: Human peripheral blood mononuclear cells (PBMCs) were isolated from a Taiwanese MDM family bearing the G to A substitution in nucleotide 256 in the SLURP1 gene, corresponding to a glycine to arginine substitution at amino acid 86 ( G86R ) in the SLURP-1 protein. PBMCs from homozygotes and wild-type controls were stimulated with anti-CD3/anti-CD28 antibodies and the level of T-cell activation was determined by the stimulation index. RESULTS: PBMCs with the heterozygous and homozygous SLURP-1 G86R mutation had defective T-cell activation. This was restored by the addition of 0 5 ug mL(-1) recombinant human SLURP-1 protein. CONCLUSIONS: Patients with MDM with the homozygous SLURP-1 G86R mutation may have an impaired T-cell activation. The presence of wild-type SLURP-1 is essential for normal T-cell activation.
20854438	[]	[]
20728296	[ "Interstitial", "deletion", "of", "13q14.13-q32.3", "presenting", "with", "Arima", "syndrome", "and", "bilateral", "retinoblastoma." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Interstitial deletion of 13q14.13-q32.3 presenting with Arima syndrome and bilateral retinoblastoma.
20728296	[ "A", "patient", "with", "a", "large", "deletion", "of", "the", "distal", "part", "of", "the", "long", "arm", "of", "chromosome", "13", "showed", "severe", "psychomotor", "retardation,", "a", "characteristic", "face,", "nystagmus,", "retinopathy,", "cystic", "kid...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	A patient with a large deletion of the distal part of the long arm of chromosome 13 showed severe psychomotor retardation, a characteristic face, nystagmus, retinopathy, cystic kidney disease, and brain malformation with molar tooth sign and cerebellar vermis hypoplasia, a phenotype typical of Arima syndrome. This patient also had bilateral retinoblastoma. Fluorescent in situ hybridization and single-nucleotide-polymorphism genotyping microarray demonstrated an interstitial deletion of 54 Mbp, ranging from 13q14.13 to 13q32.3 and involving the RB1 gene. This patient is the first case of Arima syndrome, or a Joubert syndrome-related disorder, that showed linkage to chromosome 13q.
20728296	[]	[]
20887110	[ "Impact", "of", "5,10-methylenetetrahydrofolate", "reductase", "gene", "polymorphism", "on", "neural", "tube", "defects." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Impact of 5,10-methylenetetrahydrofolate reductase gene polymorphism on neural tube defects.
20887110	[ "OBJECT:", "Neural", "tube", "defects", "(NTDs)", "are", "among", "the", "most", "common", "congenital", "malformations", "worldwide.", "Their", "etiology", "and", "exact", "mechanisms", "of", "development", "are", "incompletely", "understood.", "Many", "enzymes", "...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0...	OBJECT: Neural tube defects (NTDs) are among the most common congenital malformations worldwide. Their etiology and exact mechanisms of development are incompletely understood. Many enzymes involved in folate metabolism and the genes encoding these enzymes have been studied as candidates in their etiology. A mutation in the methylenetetrahydrofolate reductase (MTHFR) gene--a C-->T transition at nucleotide 677 --is one among them. The mutation results in substitution of alanine by valine at a functionally important site in the enzyme. It has been shown to be a risk factor for development of NTDs in certain populations. The present study was conducted to evaluate the role of MTHFR 677 C-->T mutation as a risk factor for NTD in the South Indian population and to determine the relative importance of the genotypes in the affected child and its mother. METHODS: Blood samples were collected from the test and the control groups. The test group consisted of children with NTDs and their mothers, while the control group consisted of apparently healthy controls. MTHFR C677T polymorphism in the 3 groups was determined by polymerase chain reaction and restriction fragment length polymorphism studies. Comparison of polymorphism in the 3 groups was using the chi-square test. RESULTS: There was a significant difference in the prevalence of MTHFR 677 C-->T mutation among the 3 groups (p = 0.002). The risk conferred by the TT genotype in the child was statistically significant (OR 12.625, 95% CI 1.430-111.465). In the mothers, however, although there was an increased prevalence of the mutation compared with the control individuals, the difference was not statistically significant (p = 0.152). CONCLUSIONS: The MTHFR 677TT genotype is considered to be a definite risk factor for development of NTDs. It is the TT genotype status of the developing embryo, rather than the TT genotype status of its mother, that is the critical genetic determinant of MTHFR-related NTD risk.
20887110	[]	[]
20602574	[ "Bikunin", "and", "a1-microglobulin/bikunin", "precursor", "(AMBP)", "gene", "mutational", "screening", "in", "patients", "with", "kidney", "stones:", "a", "case-control", "study." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Bikunin and a1-microglobulin/bikunin precursor (AMBP) gene mutational screening in patients with kidney stones: a case-control study.
20602574	[ "OBJECTIVE:", "Bikunin", "is", "an", "inhibitor", "of", "kidney", "stone", "formation", "synthesized", "in", "the", "liver", "together", "with", "a(1)-microglobulin", "from", "the", "a(1)-microglobulin/bikunin", "precursor", "(AMBP)", "gene.", "The", "aim", "of", "t...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	OBJECTIVE: Bikunin is an inhibitor of kidney stone formation synthesized in the liver together with a(1)-microglobulin from the a(1)-microglobulin/bikunin precursor (AMBP) gene. The aim of this study was to investigate the possible association between bikunin/AMBP gene polymorphisms and urinary stone formation. MATERIAL AND METHODS: To analyse the DNA, blood samples were taken from 75 kidney stone formers who had a familial stone history, 35 sporadic stone formers and 101 healthy individuals. Four exons of bikunin gene and five parts of the promoter region of the AMBP gene were screened using single-strand conformation polymorphism and nucleotide sequence analysis. RESULTS: The Init-2 region of the promoter of AMBP gene had polymorphisms at positions -218 and -189 nt giving three different genotypes having 1,3, 2,4 and 1,2,3,4 alleles with frequencies of 17.06%, 60.19% and 22.75%, respectively, in all groups. Therefore, the Init-2 region appears to be polymorphic. As a result, the 1,3 allele has -218G and -189T complying with the reference database sequence, the 2,4 allele has -218G and T-189C substitution and the allele 1,2,3,4 genotype has substitutions at positions G-218C and T-189C . CONCLUSIONS: There were no significant differences in allele distribution between patients and controls. These common alleles exist in the Turkish population independent of stone formation. These results are the first to demonstrate the existence of bikunin and AMBP promoter polymorphism. Although the Init-2 region of the AMBP gene is the binding site for various transcription factors, the results showed no association between these observed genotypes and stone-forming phenotypes.
20602574	[]	[]
21080147	[ "Novel", "CRELD1", "gene", "mutations", "in", "patients", "with", "atrioventricular", "septal", "defect." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Novel CRELD1 gene mutations in patients with atrioventricular septal defect.
21080147	[ "BACKGROUND:", "Atrioventricular", "septal", "defects", "(AVSDs)", "occur", "as", "clinical", "defects", "of", "several", "different", "syndromes,", "as", "autosomal", "dominant", "defects,", "and", "as", "sporadically", "occurring", "malformations.", "Consequently,", "...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	BACKGROUND: Atrioventricular septal defects (AVSDs) occur as clinical defects of several different syndromes, as autosomal dominant defects, and as sporadically occurring malformations. Consequently, there is genetic heterogeneity, but until recently, little is known about the genes involving in the pathogenesis of AVSD. CRELD1 gene, a novel cell adhesion molecule, is a candidate gene for AVSD. METHODS: This study included 133 patients with AVSD and 200 healthy controls. Peripheral blood samples were collected and genomic DNA was extracted from the leukocytes. CRELD1 was amplified by polymerase chain reaction (PCR) with specific primers. The sequences of PCR products were compared between the patients and controls. RESULTS: In a patient, a C-to-G transition was identified at nucleotide 857 in exon 8 that resulted in a substitution of alanine for proline at amino acid 286 in the first calcium-binding EGF domain. This patient had an isolated partial AVSD and the mutation was inherited from her mother. Another mutation was detected in a patient with a partial AVSD and evidence of Down syndrome. The heterozygous c.973G>A transition in exon 9 resulted in a substitution of lysine for glutamic acid at amino acid 325 ( E325K ) in the second calcium-binding EGF domain. CONCLUSIONS: Two novel CRELD1 mutations were identified in the calcium-binding EGF domain in patients with AVSD. CRELD1 is likely to be an AVSD-susceptibility gene and CRELD1 mutations may increase the risk of developing a heart defect rather than being a direct causative mutation.
21080147	[]	[]
20708777	[ "Association", "of", "DNA", "polymorphisms", "within", "the", "CYP11B2/CYP11B1", "locus", "and", "postoperative", "hypertension", "risk", "in", "the", "patients", "with", "aldosterone-producing", "adenomas." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Association of DNA polymorphisms within the CYP11B2/CYP11B1 locus and postoperative hypertension risk in the patients with aldosterone-producing adenomas.
20708777	[ "OBJECTIVES:", "Hypertension", "often", "persists", "after", "adrenalectomy", "for", "primary", "aldosteronism.", "Traditional", "factors", "associated", "with", "postoperative", "hypertension", "were", "evaluated,", "but", "whether", "genetic", "determinants", "were", "i...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	OBJECTIVES: Hypertension often persists after adrenalectomy for primary aldosteronism. Traditional factors associated with postoperative hypertension were evaluated, but whether genetic determinants were involved remains poorly understood. The aim of this study was to investigate the association of DNA polymorphisms within steroid synthesis genes (CYP11B2, CYP11B1) and the postoperative resolution of hypertension in Chinese patients undergoing adrenalectomy for aldosterone-producing adenomas (APA). METHODS: Ninety-three patients with APA were assessed for postoperative resolution of hypertension. All patients were genotyped for rs1799998 ( C-344 T ), intron 2 conversion, rs4539 ( A2718G ) within CYP11B2 and rs6410 ( G22 5A ), rs6387 ( A2803G ) within CYP11B1. The associations between CYPB11B2/CYP11B1 polymorphisms and persistent postoperative hypertension were assessed by multivariate analysis. RESULTS: CYP11B2-CYP11B1 haplotype was associated with persistent postoperative hypertension in Chinese patients undergoing adrenalectomy with APA (P = .006). Specifically, the rs4539 (AA) polymorphism was associated with persistent postoperative hypertension (P = .002). Multivariate logistic regression revealed the common haplotypes H1 (AGACT), H2 (AGAWT), and H3 (AGAWC) were associated with the persistent postoperative hypertension (P = .01, 0.03, 0.005 after Bonferroni correction). Additional predictors of persistent postoperative hypertension included duration of hypertension (P <.0005), family history of hypertension (P = .001), and elevated systolic blood pressure (P = .015). CONCLUSIONS: The rs4539 (AA), H1, H2, and H3 are genetic predictors for postoperative persistence of hypertension for Chinese patients treated by adrenalectomy with APA. DNA polymorphisms at CYP11B2/B1 locus may confer susceptibility to postoperative hypertension of patients with APA.
20708777	[]	[]
21059483	[ "The", "GALT", "rush:", "high", "carrier", "frequency", "of", "an", "unusual", "deletion", "mutation", "of", "the", "GALT", "gene", "in", "the", "Ashkenazi", "population." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	The GALT rush: high carrier frequency of an unusual deletion mutation of the GALT gene in the Ashkenazi population.
21059483	[ "Classic", "galactosemia", "is", "an", "autosomal", "recessive", "disorder", "of", "galactose", "metabolism", "manifesting", "in", "the", "first", "weeks", "of", "life", "following", "exposure", "to", "a", "milk-based", "diet.", "Despite", "the", "benefit", "of", ...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	Classic galactosemia is an autosomal recessive disorder of galactose metabolism manifesting in the first weeks of life following exposure to a milk-based diet. Despite the benefit of avoidance of lactose, many patients suffer from long-term complications including neurological deficits and ovarian failure. To date, over 230 mutations have been described in the GALT gene resulting in galactosemia. Recently, an unusual mutation was characterized causing a 5.5 kb deletion, with a relatively high carrier rate in subjects of Ashkenazi Jewish (AJ) descent. The aim of this study was to estimate the carrier frequency of this mutation in the AJ population in Israel. For this purpose we developed a high-throughput methodology to genotype both normal and deleted alleles using a chip-based matrix-assisted laser desorption-time-of-flight (MALDI-TOF) mass spectrometer and Multiplex PCR. DNA samples of 760 anonymous AJ subjects were submitted for analysis, subsequently detecting six individuals heterozygous for the GALT deletion mutation, giving a carrier frequency of 1 in 127 (0.79%). Based on these results, we suggest that the method described here provides a basis for genetic screening and prenatal counseling and can potentially reduce the morbidity and mortality associated with delayed diagnosis of galactosemia in this patient population.
21059483	[]	[]
21103668	[ "Characterisation", "of", "two", "novel", "large", "F8", "deletions", "in", "patients", "with", "severe", "haemophilia", "A", "and", "factor", "VIII", "inhibitors." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Characterisation of two novel large F8 deletions in patients with severe haemophilia A and factor VIII inhibitors.
21103668	[ "Large", "deletions", "are", "found", "in", "approximately", "5%", "of", "patients", "with", "severe", "haemophilia", "A,", "but", "only", "a", "few", "deletion", "breakpoints", "have", "been", "characterised", "precisely", "so", "far.", "In", "this", "study", ...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	Large deletions are found in approximately 5% of patients with severe haemophilia A, but only a few deletion breakpoints have been characterised precisely so far. In this study we characterised the deletion breakpoints of two patients with severe haemophilia A, large deletions and factor VIII (FVIII) inhibitors, and subsequently established deletion-specific assays for the identification of carriers. Patient 1 had a deletion of 37,410 bp comprising exon 1 and the F8 promoter region, and a 5 bp homology (GGGCC) is present at the chromosomal fusion site. In patient 2, a deletion of 22,230 bp including parts of intron 25, exon 26 and 3'-UTR was identified. No homologous repetitive elements were found at the breakpoints. However, both breakpoints were located within long terminal repeats of endogenous retroviruses and the DNA motif TTTAAA - known to be able to bend DNA molecules - was identified at the centromeric breakpoint. By deletion-specific PCR experiments we were able to identify a heterozygous state in mother 2 (carrier) while mother 1 presented only with wild-type alleles (non-carrier). Both deletions are most likely created by DNA double strand breaks and subsequent DNA repair by the non-homologous end joining DNA repair pathway (NHEJ). The exact identification of the deletion breakpoints provides a reliable diagnostic tool for carrier identification in affected families by means of a deletion-specific PCR.
21103668	[]	[]
20682662	[ "Lack", "of", "association", "of", "C-C", "chemokine", "receptor", "5", "/\\32", "deletion", "status", "with", "rheumatoid", "arthritis,", "systemic", "lupus", "erythematosus,", "lupus", "nephritis,", "and", "disease", "severity." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Lack of association of C-C chemokine receptor 5 /\32 deletion status with rheumatoid arthritis, systemic lupus erythematosus, lupus nephritis, and disease severity.
20682662	[ "OBJECTIVE:", "C-C", "chemokine", "receptor", "5", "(CCR5)", "plays", "an", "important", "role", "in", "inflammation.", "A", "32", "base-pair", "(/\\32)", "deletion", "in", "the", "CCR5", "gene", "leads", "to", "a", "nonfunctional", "receptor.", "This", "deletio...	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...	OBJECTIVE: C-C chemokine receptor 5 (CCR5) plays an important role in inflammation. A 32 base-pair (/\32) deletion in the CCR5 gene leads to a nonfunctional receptor. This deletion has been reported to have a protective effect on the development and progression of several autoimmune diseases. We investigated whether the /\32 deletion is associated with disease susceptibility in a population of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and lupus nephritis (LN); and whether it is associated with disease severity. METHODS: DNA samples from 405 RA patients, 97 SLE patients, 113 LN patients, and 431 healthy controls were genotyped for the CCR5 /\32 deletion. Differences in genotype frequencies were tested between patients and controls. Association of genotypes with disease severity was analyzed. RESULTS: Genotype frequencies of each group were in Hardy-Weinberg equilibrium. The genotype frequencies of patients did not differ significantly from controls (CCR5//\32, /\32//\32: RA 18.3% and 1.2%, respectively; SLE 17.5% and 2.1%; LN 13.3% and 1.8%; controls 20.0% and 2.8%). However, there was a trend for lower /\32 deletion allele frequency in LN patients compared to controls (p = 0.08). There was no significant association between the CCR5 status and disease severity in RA, SLE, or LN. CONCLUSION: Although an association with LN cannot be excluded, the CCR5 /\32 deletion does not seem to be a disease susceptibility genotype for RA, SLE, or LN. No significant effect of the /\32 deletion on disease severity was demonstrated.
20682662	[]	[]
20806042	[ "A", "novel", "mutation", "in", "GJA8", "causing", "congenital", "cataract-microcornea", "syndrome", "in", "a", "Chinese", "pedigree." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	A novel mutation in GJA8 causing congenital cataract-microcornea syndrome in a Chinese pedigree.

22016685

[ "A", "novel", "missense", "mutation", "Asp506Gly", " ", "in", "Exon", "13", "of", "the", "F11", "gene", "in", "an", "asymptomatic", "Korean", "woman", "with", "mild", "factor", "XI", "deficiency." ]

[ 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

A novel missense mutation Asp506Gly in Exon 13 of the F11 gene in an asymptomatic Korean woman with mild factor XI deficiency.

22016685

[ "Factor", "XI", "(FXI)", "deficiency", "is", "a", "rare", "autosomal", "recessive", "coagulation", "disorder", "most", "commonly", "found", "in", "Ashkenazi", "and", "Iraqi", "Jews,", "but", "it", "is", "also", "found", "in", "other", "ethnic", "groups.", "It"...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

Factor XI (FXI) deficiency is a rare autosomal recessive coagulation disorder most commonly found in Ashkenazi and Iraqi Jews, but it is also found in other ethnic groups. It is a trauma or surgery-related bleeding disorder, but spontaneous bleeding is rarely seen. The clinical manifestation of bleeding in FXI deficiency cases is variable and seems to poorly correlate with plasma FXI levels. The molecular pathology of FXI deficiency is mutation in the F11 gene on the chromosome band 4q35. We report a novel mutation of the F11 gene in an 18-year-old asymptomatic Korean woman with mild FXI deficiency. Pre-operative laboratory screen tests for lipoma on her back revealed slightly prolonged activated partial thromboplastin time (45.2 sec; reference range, 23.2-39.4 sec). Her FXI activity (35%) was slightly lower than the normal FXI activity (reference range, 50-150%). Direct sequence analysis of the F11 gene revealed a heterozygous A to G substitution in nucleotide 1517 ( c.1517A>G ) of exon 13, resulting in the substitution of aspartic acid with glycine in codon 506 ( p.Asp506Gly ). To the best of our knowledge, the Asp506Gly is a novel missense mutation, and this is the first genetically confirmed case of mild FXI deficiency in Korea.

22016685

[]

21850008

[ "Mutations", "in", "mitochondrially", "encoded", "complex", "I", "enzyme", "as", "the", "second", "common", "cause", "in", "a", "cohort", "of", "Chinese", "patients", "with", "mitochondrial", "myopathy,", "encephalopathy,", "lactic", "acidosis", "and", "stroke-like"...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Mutations in mitochondrially encoded complex I enzyme as the second common cause in a cohort of Chinese patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes.

21850008

[ "The", "mutation", "pattern", "of", "mitochondrial", "DNA", "(mtDNA)", "in", "mainland", "Chinese", "patients", "with", "mitochondrial", "myopathy,", "encephalopathy,", "lactic", "acidosis", "and", "stroke-like", "episodes", "(MELAS)", "has", "been", "rarely", "report...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

The mutation pattern of mitochondrial DNA (mtDNA) in mainland Chinese patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) has been rarely reported, though previous data suggested that the mutation pattern of MELAS could be different among geographically localized populations. We presented the results of comprehensive mtDNA mutation analysis in 92 unrelated Chinese patients with MELAS (85 with classic MELAS and 7 with MELAS/Leigh syndrome (LS) overlap syndrome). The mtDNA A3243G mutation was the most common causal genotype in this patient group (79/92 and 85.9%). The second common gene mutation was G13513A (7/92 and 7.6%). Additionally, we identified T10191C ( p.S45P ) in ND3, A11470C ( p. K237N ) in ND4, T13046C ( p.M237T ) in ND5 and a large-scale deletion (13025-13033:14417-14425) involving partial ND5 and ND6 subunits of complex I in one patient each. Among them, A11470C , T13046C and the single deletion were novel mutations. In summary, patients with mutations affecting mitochondrially encoded complex I (MTND) reached 12.0% (11/92) in this group. It is noteworthy that all seven patients with MELAS/LS overlap syndrome were associated with MTND mutations. Our data emphasize the important role of MTND mutations in the pathogenicity of MELAS, especially MELAS/LS overlap syndrome.

21850008

[]

22104738

[ "Novel", "compound", "heterozygous", "mutation", "of", "MLYCD", "in", "a", "Chinese", "patient", "with", "malonic", "aciduria." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Novel compound heterozygous mutation of MLYCD in a Chinese patient with malonic aciduria.

22104738

[ "A", "3-year-old", "Chinese", "boy", "presented", "with", "prominent", "clinical", "features", "of", "malonic", "aciduria,", "including", "developmental", "delay,", "short", "stature,", "brain", "abnormalities", "and", "massive", "excretion", "of", "malonic", "acid", ...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

A 3-year-old Chinese boy presented with prominent clinical features of malonic aciduria, including developmental delay, short stature, brain abnormalities and massive excretion of malonic acid and methylmalonic acid. Molecular characterization by DNA sequencing analysis and multiplex ligation-dependent probe amplification of the MLYCD gene revealed a heterozygous mutation ( c.920T>G , p.Leu307Arg ) in the patient and his father and a heterozygous deletion comprising exon 1 in the patient and his mother. The missense mutation ( c.920T>G ) was not found in 100 healthy controls and has not been reported previously. Our findings expand the number of reported cases and add a novel entry to the repertoire of MLYCD mutations.

22104738

[]

22295085

[ "Genetic", "and", "epigenetic", "alterations", "of", "the", "NF2", "gene", "in", "sporadic", "vestibular", "schwannomas." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Genetic and epigenetic alterations of the NF2 gene in sporadic vestibular schwannomas.

22295085

[ "BACKGROUND:", "Mutations", "in", "the", "neurofibromatosis", "type", "2", "(NF2)", "tumor-suppressor", "gene", "have", "been", "identified", "in", "not", "only", "NF2-related", "tumors", "but", "also", "sporadic", "vestibular", "schwannomas", "(VS).", "This", "stud...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

BACKGROUND: Mutations in the neurofibromatosis type 2 (NF2) tumor-suppressor gene have been identified in not only NF2-related tumors but also sporadic vestibular schwannomas (VS). This study investigated the genetic and epigenetic alterations in tumors and blood from 30 Korean patients with sporadic VS and correlated these alterations with tumor behavior. METHODOLOGY/PRINCIPAL FINDINGS: NF2 gene mutations were detected using PCR and direct DNA sequencing and three highly polymorphic microsatellite DNA markers were used to assess the loss of heterozygosity (LOH) from chromosome 22. Aberrant hypermethylation of the CpG island of the NF2 gene was also analyzed. The tumor size, the clinical growth index, and the proliferative activity assessed using the Ki-67 labeling index were evaluated. We found 18 mutations in 16 cases of 30 schwannomas (53%). The mutations included eight frameshift mutations, seven nonsense mutations, one in-frame deletion, one splicing donor site, and one missense mutation. Nine patients (30%) showed allelic loss. No patient had aberrant hypermethylation of the NF2 gene and correlation between NF2 genetic alterations and tumor behavior was not observed in this study. CONCLUSIONS/SIGNIFICANCE: The molecular genetic changes in sporadic VS identified here included mutations and allelic loss, but no aberrant hypermethylation of the NF2 gene was detected. In addition, no clear genotype/phenotype correlation was identified. Therefore, it is likely that other factors contribute to tumor formation and growth.

22295085

[]

22174939

[ "RET", "mutational", "spectrum", "in", "Hirschsprung", "disease:", "evaluation", "of", "601", "Chinese", "patients." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients.

22174939

[ "Rare", "(RVs)", "and", "common", "variants", "of", "the", "RET", "gene", "contribute", "to", "Hirschsprung", "disease", "(HSCR;", "congenital", "aganglionosis).", "While", "RET", "common", "variants", "are", "strongly", "associated", "with", "the", "commonest", "...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

Rare (RVs) and common variants of the RET gene contribute to Hirschsprung disease (HSCR; congenital aganglionosis). While RET common variants are strongly associated with the commonest manifestation of the disease (males; short-segment aganglionosis; sporadic), rare coding sequence (CDS) variants are more frequently found in the lesser common and more severe forms of the disease (females; long/total colonic aganglionosis; familial).Here we present the screening for RVs in the RET CDS and intron/exon boundaries of 601 Chinese HSCR patients, the largest number of patients ever reported. We identified 61 different heterozygous RVs (50 novel) distributed among 100 patients (16.64%). Those include 14 silent, 29 missense, 5 nonsense, 4 frame-shifts, and one in-frame amino-acid deletion in the CDS, two splice-site deletions, 4 nucleotide substitutions and a 22-bp deletion in the intron/exon boundaries and 1 single-nucleotide substitution in the 5' untranslated region. Exonic variants were mainly clustered in RET the extracellular domain. RET RVs were more frequent among patients with the most severe phenotype (24% vs. 15% in short-HSCR). Phasing RVs with the RET HSCR-associated haplotype suggests that RVs do not underlie the undisputable association of RET common variants with HSCR. None of the variants were found in 250 Chinese controls.

22174939

[]

21943124

[ "A", "deletion", "of", "FGFR2", "creating", "a", "chimeric", "IIIb/IIIc", "exon", "in", "a", "child", "with", "Apert", "syndrome." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

A deletion of FGFR2 creating a chimeric IIIb/IIIc exon in a child with Apert syndrome.

21943124

[ "BACKGROUND:", "Signalling", "by", "fibroblast", "growth", "factor", "receptor", "type", "2", "(FGFR2)", "normally", "involves", "a", "tissue-specific", "alternative", "splice", "choice", "between", "two", "exons", "(IIIb", "and", "IIIc),", "which", "generates", "tw...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

BACKGROUND: Signalling by fibroblast growth factor receptor type 2 (FGFR2) normally involves a tissue-specific alternative splice choice between two exons (IIIb and IIIc), which generates two receptor isoforms (FGFR2b and FGFR2c respectively) with differing repertoires of FGF-binding specificity. Here we describe a unique chimeric IIIb/c exon in a patient with Apert syndrome, generated by a non-allelic homologous recombination event. CASE PRESENTATION: We present a child with Apert syndrome in whom routine genetic testing had excluded the FGFR2 missense mutations commonly associated with this disorder. The patient was found to harbour a heterozygous 1372 bp deletion between FGFR2 exons IIIb and IIIc, apparently originating from recombination between 13 bp of identical DNA sequence present in both exons. The rearrangement was not present in the unaffected parents. CONCLUSIONS: Based on the known pathogenesis of Apert syndrome, the chimeric FGFR2 protein is predicted to act in a dominant gain-of-function manner. This is likely to result from its expression in mesenchymal tissues, where retention of most of the residues essential for FGFR2b binding activity would result in autocrine activation. This report adds to the repertoire of rare cases of Apert syndrome for which a pathogenesis based on atypical FGFR2 rearrangements can be demonstrated.

21943124

[]

21779184

[ "Detection", "of", "a-thalassemia-1", "Southeast", "Asian", "and", "Thai", "type", "deletions", "and", "b-thalassemia", "3.5-kb", "deletion", "by", "single-tube", "multiplex", "real-time", "PCR", "with", "SYBR", "Green1", "and", "high-resolution", "melting", "analysis...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Detection of a-thalassemia-1 Southeast Asian and Thai type deletions and b-thalassemia 3.5-kb deletion by single-tube multiplex real-time PCR with SYBR Green1 and high-resolution melting analysis.

21779184

[ "BACKGROUND:", "Prevention", "and", "control", "of", "thalassemia", "requires", "simple,", "rapid,", "and", "accurate", "screening", "tests", "for", "carrier", "couples", "who", "are", "at", "risk", "of", "conceiving", "fetuses", "with", "severe", "thalassemia.", ...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

BACKGROUND: Prevention and control of thalassemia requires simple, rapid, and accurate screening tests for carrier couples who are at risk of conceiving fetuses with severe thalassemia. METHODS: Single-tube multiplex real-time PCR with SYBR Green1 and high-resolution melting (HRM) analysis were used for the identification of a-thalassemia-1 Southeast Asian (SEA) and Thai type deletions and b-thalassemia 3.5-kb gene deletion. The results were compared with those obtained using conventional gap-PCR. DNA samples were derived from 28 normal individuals, 11 individuals with a-thalassemia-1 SEA type deletion, 2 with a-thalassemia-1 Thai type deletion, and 2 with heterozygous b-thalassemia 3.5-kb gene deletion. RESULTS: HRM analysis indicated that the amplified fragments from a-thalassemia-1 SEA type deletion, a-thalassemia-1 Thai type deletion, b-thalassemia 3.5-kb gene deletion, and the wild-type b-globin gene had specific peak heights at mean melting temperature (T(m)) values of 86.89 , 85.66 , 77.24 , and 74.92 , respectively. The results obtained using single-tube multiplex real-time PCR with SYBR Green1 and HRM analysis showed 100% consistency with those obtained using conventional gap-PCR. CONCLUSIONS: Single-tube multiplex real-time PCR with SYBR Green1 and HRM analysis is a potential alternative for routine clinical screening of the common types of a- and b-thalassemia large gene deletions, since it is simple, cost-effective, and highly accurate.

21779184

[]

21640722

[ "Xeroderma", "pigmentosum", "variant:", "complementary", "molecular", "approaches", "to", "detect", "a", "13", "base", "pair", "deletion", "in", "the", "DNA", "polymerase", "eta", "gene." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Xeroderma pigmentosum variant: complementary molecular approaches to detect a 13 base pair deletion in the DNA polymerase eta gene.

21640722

[ "Deficiencies", "of", "DNA", "polymerase", "eta-an", "enzyme", "mediating", "replication", "past", "UV-induced", "DNA", "damage-predispose", "individuals", "to", "xeroderma", "pigmentosum", "variant", "(XPV)", "and", "result", "in", "a", "high", "incidence", "of", "...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

Deficiencies of DNA polymerase eta-an enzyme mediating replication past UV-induced DNA damage-predispose individuals to xeroderma pigmentosum variant (XPV) and result in a high incidence of skin cancers. We designed, developed and assessed several complementary molecular approaches to detect a genetically inherited deletion within DNA polymerase eta. RNA was reverse transcribed from XPV fibroblasts and from normal human cells, and standard polymerase chain reaction (PCR) was conducted on the cDNA targeting a region with a 13 base pair deletion within the polymerase eta gene. PCR products were subjected to restriction fragment length polymorphism (RFLP) analysis and cycle DNA sequencing. The deletion was found to eliminate a BsrGI restriction site and affected the number of resultant fragments visualized after gel electrophoresis. Cycle sequencing of polymerase eta-specific amplicons from XPV and normal cells provided a second approach for detecting the mutation. Additionally, the use of a fluorescent nucleic acid dye-EvaGreen-in real-time PCR and melt curve analysis distinguished normal and XPV patient-derived amplicons as well as heteroduplexes that represent heterozygotic carriers without the need for high resolution melt analysis-compatible software. Our approaches are easily adaptable by diagnostic laboratories that screen for or verify genetically inherited disorders and identify carriers of a defective gene.

21640722

[]

21499297

[ "C10ORF97", "is", "a", "novel", "tumor-suppressor", "gene", "of", "non-small-cell", "lung", "cancer", "and", "a", "functional", "variant", "of", "this", "gene", "increases", "the", "risk", "of", "non-small-cell", "lung", "cancer." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

C10ORF97 is a novel tumor-suppressor gene of non-small-cell lung cancer and a functional variant of this gene increases the risk of non-small-cell lung cancer.

21499297

[ "In", "an", "earlier", "study", "we", "showed", "that", "C10ORF97", "(chromosome-10,", "open", "reading", "frame-97)", "was", "expressed", "in", "almost", "all", "of", "the", "tissues", "and", "cell", "lines", "tested,", "and", "that", "it", "inhibited", "the"...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

In an earlier study we showed that C10ORF97 (chromosome-10, open reading frame-97) was expressed in almost all of the tissues and cell lines tested, and that it inhibited the growth of seven tumor cell lines, including two lung carcinoma cell lines (A549 and PG). Here, we show that C10ORF97 is downregulated in non-small-cell lung cancer (NSCLC) tissue compared with normal lung tissue. Overexpression of C10ORF97 significantly suppressed human lung carcinoma A549 cell growth (proliferation and anchorage-independent growth in soft agar) and motility (migration and adhesion). This tumor-suppressive function of C10ORF97 was also verified in vivo. We further found that C10ORF97 caused G(1) arrest of A549 cells and modulated the expression level of several cell-cycle regulators (such as CDK2, cyclin-E and p27). These effects of C10ORF97 were mediated by physical association between C10ORF97 and Jun-activating domain-binding protein-1 (JAB1), and blocking of JAB1-mediated translocation of p27 from the nucleus to the cytoplasm. Together, these results indicated that C10ORF97 functions as a novel tumor suppressor by modulating several key G(1)/S-regulatory proteins by interacting with JAB1. These findings led us to hypothesize that a single-nucleotide polymorphism (SNP) in the C10ORF97 gene that affects its expression might be associated with susceptibility to NSCLC. SNP216 C>T ( rs2297882 ) in the C10ORF97 Kozak sequence was identified, and allele T of SNP216 suppressed C10ORF97 expression in vitro and in vivo. Furthermore, the TT genotype of SNP216 was associated with an increased risk of NSCLC (adjusted odds ratio=1.73 (95% confidence interval: 1.33-2.25), P=4.6 10(-5)). These data indicated that C10ORF97 is a tumor suppressor of NSCLC progression and C10ORF97-SNP216 may serve as a predictor of NSCLC.

21499297

[]

21695597

[ "MHC", "region", "and", "risk", "of", "systemic", "lupus", "erythematosus", "in", "African", "American", "women." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

MHC region and risk of systemic lupus erythematosus in African American women.

21695597

[ "The", "major", "histocompatibility", "complex", "(MHC)", "on", "chromosome", "6p21", "is", "a", "key", "contributor", "to", "the", "genetic", "basis", "of", "systemic", "lupus", "erythematosus", "(SLE).", "Although", "SLE", "affects", "African", "Americans", "dis...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

The major histocompatibility complex (MHC) on chromosome 6p21 is a key contributor to the genetic basis of systemic lupus erythematosus (SLE). Although SLE affects African Americans disproportionately compared to European Americans, there has been no comprehensive analysis of the MHC region in relationship to SLE in African Americans. We conducted a screening of the MHC region for 1,536 single nucleotide polymorphisms (SNPs) and the deletion of the C4A gene in a SLE case-control study (380 cases, 765 age-matched controls) nested within the prospective Black Women's Health Study. We also genotyped 1,509 ancestral informative markers throughout the genome to estimate European ancestry to control for population stratification due to population admixture. The most strongly associated SNP with SLE was the rs9271366 (odds ratio, OR = 1.70, p = 5.6 10(-5)) near the HLA-DRB1 gene. Conditional haplotype analysis revealed three other SNPs, rs204890 (OR = 1.86, p = 1.2 10(-4)), rs2071349 (OR = 1.53, p = 1.0 10(-3)), and rs2844580 (OR = 1.43, p = 1.3 10(-3)), to be associated with SLE independent of the rs9271366 SNP. In univariate analysis, the OR for the C4A deletion was 1.38, p = 0.075, but after simultaneous adjustment for the other four SNPs the odds ratio was 1.01, p = 0.98. A genotype score combining the four newly identified SNPs showed an additive risk according to the number of high-risk alleles (OR = 1.67 per high-risk allele, p < 0.0001). Our strongest signal, the rs9271366 SNP, was also associated with higher risk of SLE in a previous Chinese genome-wide association study (GWAS). In addition, two SNPs found in a GWAS of European ancestry women were confirmed in our study, indicating that African Americans share some genetic risk factors for SLE with European and Chinese subjects. In summary, we found four independent signals in the MHC region associated with risk of SLE in African American women.

21695597

[]

21629979

[ "Molecular", "and", "clinical", "analysis", "of", "glioblastoma", "with", "an", "oligodendroglial", "component", "(GBMO)." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Molecular and clinical analysis of glioblastoma with an oligodendroglial component (GBMO).

21629979

[ "The", "genetic", "and", "clinical", "features", "of", "glioblastoma", "with", "an", "oligodendroglial", "component", "(GBMO),", "pathologically", "defined", "as", "anaplastic", "oligo-astrocytoma", "with", "necrosis,", "remain", "unclear.", "We", "investigated", "the",...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

The genetic and clinical features of glioblastoma with an oligodendroglial component (GBMO), pathologically defined as anaplastic oligo-astrocytoma with necrosis, remain unclear. We investigated the correlation between genetic alterations and clinical outcomes in 19 GBMO patients we have encountered since 1997. Using single nucleotide polymorphism oligonucleotide genomic (SNP) microarrays, we analyzed gene amplification, loss of heterozygosity (LOH), and homozygous deletions in their whole genome. We also analyzed their overall survival (OS). Pathological studies revealed the presence of calcification in 11 and of a cyst in 9 of the 19 patients. Whole-genome analysis using SNP microarrays revealed LOH of chromosome 10 in 11, EGFR amplification in 8, 9p21 (INK4 locus) deletion in 12, PDGFR amplification in 2, and LOH of 1p19q in 2 patients. Median OS was 14 months (average 22.8 months). The pattern of genetic alterations was similar in GBMO and glioblastoma multiforme (GBM) patients, and the clinical outcomes were similar in GBMO and GBM patients.

21629979

[]

22048266

[ "Exploratory", "investigation", "on", "functional", "significance", "of", "ETS2", "and", "SIM2", "genes", "in", "Down", "syndrome." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Exploratory investigation on functional significance of ETS2 and SIM2 genes in Down syndrome.

22048266

[ "Trisomy", "of", "the", "21{st}", "chromosome", "leads", "to", "an", "over", "dosage", "of", "several", "regulatory", "genes", "in", "Down", "syndrome", "(DS).", "Though", "allelic", "and", "genotypic", "combinations", "formed", "between", "genes", "are", "inter...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

Trisomy of the 21{st} chromosome leads to an over dosage of several regulatory genes in Down syndrome (DS). Though allelic and genotypic combinations formed between genes are interesting, till date, this particular area has never been explored in DS. In the present investigation four SNPs in two transcription factors, Single minded 2 (SIM2) and V-ets erythroblastosis virus E26 oncogene homolog2 (ETS2), located in the 21{st} chromosome were genotyped to understand their role in DS. Genomic DNA of eastern Indian probands with DS (N=132), their parents (N=209) and ethnically matched controls (N=149) was subjected to PCR-based analyses of functionally important SNPs followed by statistical analyses. ETS2 rs461155 showed high heterozygosity in DS. Significantly lower frequency of SIM2 C-G haplotype ( rs2073601 - rs2073416 ) was noticed in individuals with DS (P value =0.01669) and their fathers (P value=0.01185). Significantly lower frequency of the A-C-C-G with higher frequency of A-C-A-G haplotypes was also noticed in subjects with DS (P value =0.02089 and 0.00588 respectively). Data obtained indicate that the rs2073601 'A' allele, responsible for nonsynonymous substitution of leucine to methionine, may have some role in DS in this population.

22048266

[]

22028770

[ "APOE", "genotype-function", "relationship:", "evidence", "of", "-491", "A/T", " ", "promoter", "polymorphism", "modifying", "transcription", "control", "but", "not", "type", "2", "diabetes", "risk." ]

[ 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

APOE genotype-function relationship: evidence of -491 A/T promoter polymorphism modifying transcription control but not type 2 diabetes risk.

22028770

[ "BACKGROUND:", "The", "apolipoprotein", "E", "gene", "(APOE)", "coding", "polymorphism", "modifies", "the", "risks", "of", "Alzheimer's", "disease,", "type", "2", "diabetes,", "and", "coronary", "heart", "disease.", "Aside", "from", "the", "coding", "variants,", "...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

BACKGROUND: The apolipoprotein E gene (APOE) coding polymorphism modifies the risks of Alzheimer's disease, type 2 diabetes, and coronary heart disease. Aside from the coding variants, single nucleotide polymorphism (SNP) of the APOE promoter has also been shown to modify the risk of Alzheimer's disease. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigate the genotype-function relationship of APOE promoter polymorphism at molecular level and at physiological level: i.e., in transcription control of the gene and in the risk of type 2 diabetes. In molecular studies, the effect of the APOE -491A/T ( rs449647 ) polymorphism on gene transcription was accessed by dual-luciferase reporter gene assays. The -491 A to T substitution decreased the activity (p<0.05) of the cloned APOE promoter (-1017 to +406). Using the -501 to -481 nucleotide sequence of the APOE promoter as a 'bait' to screen the human brain cDNA library by yeast one-hybrid system yielded ATF4, an endoplasmic reticulum stress response gene, as one of the interacting factors. Electrophoretic-mobility-shift assays (EMSA) and chromatin immuno-precipitation (ChIP) analyses further substantiated the physical interaction between ATF4 and the APOE promoter. Over-expression of ATF4 stimulated APOE expression whereas siRNA against ATF4 suppressed the expression of the gene. However, interaction between APOE promoter and ATF4 was not -491A/T -specific. At physiological level, the genotype-function relationship of APOE promoter polymorphism was studied in type 2 diabetes. In 630 cases and 595 controls, three APOE promoter SNPs -491A/T , -219G/T ( rs405509 ), and +113G/C ( rs440446 ) were genotyped and tested for association with type 2 diabetes in Hong Kong Chinese. No SNP or haplotype association with type 2 diabetes was detected. CONCLUSIONS/SIGNIFICANCE: At molecular level, polymorphism -491A/T and ATF4 elicit independent control of APOE gene expression. At physiological level, no genotype-risk association was detected between the studied APOE promoter SNPs and type 2 diabetes in Hong Kong Chinese.

22028770

[]

21771880

[ "Resequencing", "of", "IRS2", "reveals", "rare", "variants", "for", "obesity", "but", "not", "fasting", "glucose", "homeostasis", "in", "Hispanic", "children." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Resequencing of IRS2 reveals rare variants for obesity but not fasting glucose homeostasis in Hispanic children.

21771880

[ "Our", "objective", "was", "to", "resequence", "insulin", "receptor", "substrate", "2", "(IRS2)", "to", "identify", "variants", "associated", "with", "obesity-", "and", "diabetes-related", "traits", "in", "Hispanic", "children.", "Exonic", "and", "intronic", "segmen...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

Our objective was to resequence insulin receptor substrate 2 (IRS2) to identify variants associated with obesity- and diabetes-related traits in Hispanic children. Exonic and intronic segments, 5' and 3' flanking regions of IRS2 ( 14.5 kb), were bidirectionally sequenced for single nucleotide polymorphism (SNP) discovery in 934 Hispanic children using 3730XL DNA Sequencers. Additionally, 15 SNPs derived from Illumina HumanOmni1-Quad BeadChips were analyzed. Measured genotype analysis tested associations between SNPs and obesity and diabetes-related traits. Bayesian quantitative trait nucleotide analysis was used to statistically infer the most likely functional polymorphisms. A total of 140 SNPs were identified with minor allele frequencies (MAF) ranging from 0.001 to 0.47. Forty-two of the 70 coding SNPs result in nonsynonymous amino acid substitutions relative to the consensus sequence; 28 SNPs were detected in the promoter, 12 in introns, 28 in the 3'-UTR, and 2 in the 5'-UTR. Two insertion/deletions (indels) were detected. Ten independent rare SNPs (MAF = 0.001-0.009) were associated with obesity-related traits (P = 0.01-0.00002). SNP 10510452_139 in the promoter region was shown to have a high posterior probability (P = 0.77-0.86) of influencing BMI, fat mass, and waist circumference in Hispanic children. SNP 10510452_139 contributed between 2 and 4% of the population variance in body weight and composition. None of the SNPs or indels were associated with diabetes-related traits or accounted for a previously identified quantitative trait locus on chromosome 13 for fasting serum glucose. Rare but not common IRS2 variants may play a role in the regulation of body weight but not an essential role in fasting glucose homeostasis in Hispanic children.

21771880

[]

21790735

[ "A", "large", "heterozygous", "deletion", "including", "the", "entire", "C1", "inhibitor", "gene", "in", "a", "sporadic", "case", "of", "hereditary", "angio-oedema." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

A large heterozygous deletion including the entire C1 inhibitor gene in a sporadic case of hereditary angio-oedema.

21790735

[ "C1", "inhibitor", "(C1-INH)", "deficiency", "[hereditary", "or", "acquired", "angio-oedema", "(HAE", "or", "AAE)]", "is", "characterized", "by", "recurring", "episodes", "of", "subcutaneous", "or", "submucosal", "oedema.", "Many", "different", "mutations", "in", "t...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

C1 inhibitor (C1-INH) deficiency [hereditary or acquired angio-oedema (HAE or AAE)] is characterized by recurring episodes of subcutaneous or submucosal oedema. Many different mutations in the C1-INH gene have been identified as a cause of HAE. We investigated the molecular basis of the disease in a Japanese woman with sporadic HAE. Direct sequencing of genomic DNA revealed no point mutation in the C1-INH gene. Quantitative real-time PCR showed that the copy number of the C1-INH gene in the patient was half that of a healthy control. Furthermore, we identified a 650-kbp deletion on the chromosome, which included the C1-INH gene. We evaluated the correlation between the patient's attacks and her coagulation activity. The levels of D-dimer were high during the angio-oedema attacks, and often exceeded the normal range even during remission, thus the level of D-dimer reflected the activity of HAE in this patient.

21790735

[]

21506149

[ "Phenotype", "of", "the", "202", "adenine", "deletion", "in", "the", "parkin", "gene:", "40", "years", "of", "follow-up." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Phenotype of the 202 adenine deletion in the parkin gene: 40 years of follow-up.

21506149

[ "BACKGROUND:", "We", "describe", "the", "four", "decades", "follow-up", "of", "14", "parkin", "patients", "belonging", "to", "two", "large", "eight-generation-long", "in-bred", "Muslim-Arab", "kindreds.", "RESULTS:", "All", "patients", "had", "a", "single", "base-pa...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

BACKGROUND: We describe the four decades follow-up of 14 parkin patients belonging to two large eight-generation-long in-bred Muslim-Arab kindreds. RESULTS: All patients had a single base-pair of adenine deletion at nucleotide 202 of exon 2 (202A) of the parkin gene (all homozygous, one heterozygous). Parkinson's disease onset age was 17-68 years. Special features were intractable axial symptoms (low back pain, scoliosis, camptocormia, antecollis), postural tremor, and preserved cognition. CONCLUSIONS: The 202A deletion of the parkin gene causes early-onset Parkinson's disease with marked levodopa/STN-DBS-resistant axial features. Postural tremor and preserved cognition, even after 40 years of disease, were also evident.

21506149

[]

21904390

[ "Two", "novel", "mutations", "of", "the", "PAX6", "gene", "causing", "different", "phenotype", "in", "a", "cohort", "of", "Chinese", "patients." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Two novel mutations of the PAX6 gene causing different phenotype in a cohort of Chinese patients.

21904390

[ "PURPOSE:", "Aniridia", "(AN)", "is", "a", "rare", "congenital", "panocular", "disorder", "caused", "by", "the", "mutations", "of", "the", "paired", "box", "homeotic", "gene", "6(PAX6)", "gene.", "The", "PAX6gene", "is", "also", "involved", "in", "other", "ant...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

PURPOSE: Aniridia (AN) is a rare congenital panocular disorder caused by the mutations of the paired box homeotic gene 6(PAX6) gene. The PAX6gene is also involved in other anterior segment malformations including Peters anomaly. We studied the PAX6gene mutations in a cohort of affected individuals with different clinical phenotype including AN, coloboma of iris and choroid, or anterior segment malformations. PATIENTS AND METHODS: Six unrelated families and 10 sporadic patients were examined clinically. After informed consent was obtained, genomic DNA was extracted from the venous blood of all participants. Mutation screening of all exons of the PAX6gene was performed by direct sequencing of PCR-amplified DNA fragments. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect large deletions. RESULTS: By clinical examination, the patients and the pedigrees were divided into the following three groups: AN, coloboma of iris and choroids, and the anterior segment malformations including peters anomaly. Sequencing of the PAX6gene, three intragenic mutations including a novel heterozygous splicing-site mutations c.357-3C>G ( p.Ser119fsX ) were identified in the patients of the AN group. A novel missense mutation c.643T>C ( p.S216P ) was detected in the anterior segment malformation group. The mutation p.S216P located in the homeodomain region of the PAX6 caused the phenotype of Peters anomaly in family A6 with different expressing. Through MLPA analysis, a large deletion including the whole PAX6gene and DKFZ p686k1684gene was detected in one sporadic patient from the AN group. Neither intragenic mutation nor large deletion was identified in the group with coloboma of iris and choroid. CONCLUSION: Our findings further confirmed that different kind of mutations might cause different ocular phenotype, and clearly clinical phenotype classification might increase the mutation detection rate of the PAX6gene.

21904390

[]

21496008

[ "Screening", "and", "cell-based", "assessment", "of", "mutations", "in", "the", "Aristaless-related", "homeobox", "(ARX)", "gene." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Screening and cell-based assessment of mutations in the Aristaless-related homeobox (ARX) gene.

21496008

[ "ARX", "mutations", "cause", "a", "diverse", "spectrum", "of", "human", "disorders,", "ranging", "from", "severe", "brain", "and", "genital", "malformations", "to", "non-syndromic", "intellectual", "disability", "(ID).", "ARX", "is", "a", "transcription", "factor", ...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1...

ARX mutations cause a diverse spectrum of human disorders, ranging from severe brain and genital malformations to non-syndromic intellectual disability (ID). ARX is a transcription factor with multiple domains that include four polyalanine (pA) tracts, the first two of which are frequently expanded by mutations. We progressively screened DNA samples from 613 individuals with ID initially for the most frequent ARX mutations ( c.304ins(GCG) (7)'expansion' of pA1 and c.429_452dup ' dup24bp ' of pA2). Five hundred samples without pA1 or pA2 mutations had the entire ARX ORF screened by single stranded polymorphism conformation (SSCP) and/or denaturing high pressure liquid chromatography (dHPLC) analysis. Overall, eight families with six mutations in ARX were identified (1.31%): five duplication mutations in pA2 (0.82%) with three new clinical reports of families with the dup24bp and two duplications larger than the dup24bp mutation discovered ( dup27bp , dup33bp ); and three point mutations (0.6%), including one novel mutation in the homeodomain ( c.1074G>T ). Four ultraconserved regions distal to ARX (uc466-469) were also screened in a subset of 94 patients, with three unique nucleotide changes identified in two (uc466, uc467). The subcellular localization of full length ARX proteins was assessed for 11 variants. Protein mislocalization increased as a function of pA2 tract length and phenotypic severity, as has been previously suggested for pA1. Similarly, protein mislocalization of the homeodomain mutations also correlated with clinical severity, suggesting an emerging genotype vs cellular phenotype correlation.

21496008

[]

21717135

[ "Variation", "in", "genotype", "and", "higher", "virulence", "of", "a", "strain", "of", "Sporothrix", "schenckii", "causing", "disseminated", "cutaneous", "sporotrichosis." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Variation in genotype and higher virulence of a strain of Sporothrix schenckii causing disseminated cutaneous sporotrichosis.

21717135

[ "Sporotrichosis", "is", "usually", "a", "localized,", "lymphocutaneous", "disease,", "but", "its", "disseminated", "type", "was", "rarely", "reported.", "The", "main", "objective", "of", "this", "study", "was", "to", "identify", "specific", "DNA", "sequence", "var...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

Sporotrichosis is usually a localized, lymphocutaneous disease, but its disseminated type was rarely reported. The main objective of this study was to identify specific DNA sequence variation and virulence of a strain of Sporothrix schenckii isolated from the lesion of disseminated cutaneous sporotrichosis. We confirmed this strain to be S. schenckii by( ) tubulin and chitin synthase gene sequence analysis in addition to the routine mycological and partial ITS and NTS sequencing. We found a 10-bp deletion in the ribosomal NTS region of this strain, in reference to the sequence of control strains isolated from fixed cutaneous sporotrichosis. After inoculated into immunosuppressed mice, this strain caused more extensive system involvement and showed stronger virulence than the control strain isolated from a fixed cutaneous sporotrichosis. Our study thus suggests that different clinical manifestation of sporotrichosis may be associated with variation in genotype and virulence of the strain, independent of effects due to the immune status of the host.

21717135

[]

21976953

[ "Identification", "of", "a", "novel", "FBN1", "gene", "mutation", "in", "a", "Chinese", "family", "with", "Marfan", "syndrome." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Identification of a novel FBN1 gene mutation in a Chinese family with Marfan syndrome.

21976953

[ "PURPOSE:", "To", "identify", "the", "mutation", "in", "the", "fibrillin-1", "gene", "(FBN1)", "in", "a", "Chinese", "family", "with", "Marfan", "syndrome", "(MFS).", "METHODS:", "Patients", "and", "family", "members", "were", "given", "complete", "physical,", "...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

PURPOSE: To identify the mutation in the fibrillin-1 gene (FBN1) in a Chinese family with Marfan syndrome (MFS). METHODS: Patients and family members were given complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA was extracted from leukocytes of venous blood of six individuals in the family and 170 healthy Chinese individuals. All of the 65 coding exons and their flanking intronic boundaries of FBN1 were amplified in the proband by polymerase chain reaction and followed by direct sequencing. The mutation identified in the proband was screened in the other family members and the 170 healthy Chinese individuals by direct sequencing. Protein conservation analysis was performed in six species using an online ClustalW tool. Protein structure was modeled based on the Protein data bank and mutated in DeepView v4.0.1 to predict the functional consequences of the mutation. RESULTS: A novel heterozygous c.3703T>C change in exon 29 of FBN1 was detected in the proband, which resulted in the substitution of serine by proline at codon 1235 ( p.S1235P ). This mutation was also present in two family members but absent in the other, unaffected family members and the 170 healthy Chinese individuals. The mutant residue located in the calcium binding epidermal growth factor-like#15 domain is highly conserved among mammalian species and could probably induce conformation change of the domain. CONCLUSIONS: We indentified a novel p.S1235P mutation in FBN1, which is the causative mutation for MFS in this family. Our result expands the mutation spectrum of FBN1 and contributes to the study of the molecular pathogenesis of Marfan syndrome.

21976953

[]

21546516

[ "The", "57", "kb", "deletion", "in", "cystinosis", "patients", "extends", "into", "TRPV1", "causing", "dysregulation", "of", "transcription", "in", "peripheral", "blood", "mononuclear", "cells." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

The 57 kb deletion in cystinosis patients extends into TRPV1 causing dysregulation of transcription in peripheral blood mononuclear cells.

21546516

[ "BACKGROUND:", "Cystinosis", "is", "an", "autosomal", "recessive", "disease", "characterised", "by", "the", "abnormal", "accumulation", "of", "lysosomal", "cystine.", "Mutations", "in", "the", "cystinosin", "gene", "(CTNS)", "represent", "known", "causes", "for", "t...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

BACKGROUND: Cystinosis is an autosomal recessive disease characterised by the abnormal accumulation of lysosomal cystine. Mutations in the cystinosin gene (CTNS) represent known causes for the disease. The major cystinosis mutation is a 57 kb deletion on human chromosome 17p13 that removes the majority of CTNS and the entire adjacent gene, CARKL/SHPK. OBJECTIVES: In order to identify other genes that may influence the cystinosis pathobiological pathway, peripheral blood mononuclear cells (PBMC) were collected from cystinosis family members, and DNA and RNA extracted. RESULTS: Using whole genome transcriptional profiling, transient receptor potential vanilloid 1 (TRPV1) was found to be differentially expressed in association with cystinosis. This was verified using TaqMan qRT-PCR. There was a 72% reduction in PBMC TRPV1 mRNA levels in cystinosis individuals homozygous for the 57 kb deletion (n=6) compared to unaffected individuals without the deletion (n=6) (p=0.002). TRPV1 is a sensory receptor located on chromosome 17p13, adjacent to CARKL/SHPK. It was ascertained that the 57 kb deletion extends from exon 10 of CTNS, upstream through CARKL/SHPK, to intron 2 of TRPV1, thus deleting the first two non-coding exons. CONCLUSION: This is the first study to report that the 57 kb deletion extends into the TRPV1 gene causing dysregulation of transcription in PBMC isolated from cystinosis patients.

21546516

[]

21799811

[ "Strong", "association", "of", "677", "C>T", " ", "substitution", "in", "the", "MTHFR", "gene", "with", "male", "infertility--a", "study", "on", "an", "indian", "population", "and", "a", "meta-analysis." ]

[ 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Strong association of 677 C>T substitution in the MTHFR gene with male infertility--a study on an indian population and a meta-analysis.

21799811

[ "BACKGROUND:", "Methylenetetrahydrofolate", "reductase", "(MTHFR)", "is", "an", "important", "enzyme", "of", "folate", "and", "methionine", "metabolism,", "making", "it", "crucial", "for", "DNA", "synthesis", "and", "methylation.", "The", "objective", "of", "this", ...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate and methionine metabolism, making it crucial for DNA synthesis and methylation. The objective of this study was to analyze MTHFR gene 677C>T polymorphism in infertile male individuals from North India, followed by a meta-analysis on our data and published studies. METHODOLOGY/PRINCIPAL FINDINGS: We undertook genotyping on a total of 837 individuals including well characterized infertile (N=522) and confirmed fertile (N=315) individuals. The SNP was typed by direct DNA sequencing. Chi square test was done for statistical analysis. Published studies were searched using appropriate keywords. Source of data collection for meta-analysis included 'Pubmed', 'Ovid' and 'Google Scholar'. Those studies analyzing 677C>T polymorphism in male infertility and presenting all relevant data were included in meta-analysis. The genotype data for infertile subjects and fertile controls was extracted from each study. Chi square test was done to obtain odds ratio (OR) and p-value. Meta-analysis was performed using Comprehensive Meta-analysis software (Version 2). The frequency of mutant (T) allele (p=0.0025) and genotypes (CT+TT) (p=0.0187) was significantly higher in infertile individuals in comparison to fertile controls in our case-control study. The overall summary estimate (OR) for allele and genotype meta-analysis were 1.304 (p=0.000), 1.310 (p=0.000), respectively, establishing significant association of 677C>T polymorphism with male infertility. CONCLUSIONS/SIGNIFICANCE: 677C>T substitution associated strongly with male infertility in Indian population. Allele and genotype meta-analysis also supported its strong correlation with male infertility, thus establishing it as a risk factor.

21799811

[]

21976404

[ "Angiotensin-converting", "enzyme", "(ACE)", "serum", "levels", "and", "gene", "polymorphism", "in", "Egyptian", "patients", "with", "systemic", "lupus", "erythematosus." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Angiotensin-converting enzyme (ACE) serum levels and gene polymorphism in Egyptian patients with systemic lupus erythematosus.

21976404

[ "OBJECTIVES:", "To", "investigate", "the", "association", "of", "angiotensin-converting", "enzyme", "(ACE)", "gene", "polymorphism", "and", "serum", "ACE", "level", "among", "Egyptian", "SLE", "patients", "and", "its", "relation", "to", "disease", "activity", "param...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

OBJECTIVES: To investigate the association of angiotensin-converting enzyme (ACE) gene polymorphism and serum ACE level among Egyptian SLE patients and its relation to disease activity parameters. SUBJECTS AND METHODS: We enrolled 50 Egyptian female systemic lupus erythematosus (SLE) patients and 29 healthy controls. Measurement of serum ACE level was done using ELISA, and the ACE genotype was determined by polymerase chain reaction using genomic DNA from peripheral blood. RESULTS: A significant difference was found in ACE genotypes between SLE patients and controls ( (2 )= 7.84, p = 0.02). The frequency of ACE DD versus (DI and II) genotypes was significantly higher in SLE patients compared with controls ( (2 )= 5.57, p = 0.018 and OR for risk of SLE was 3.1 with 95% confidence interval: 1.198.06). Mean serum ACE level was significantly higher in the SLE group compared with controls (p = 0.006). Subjects with DD genotype had a significantly higher mean level than those with DI (p = 0.015) and II genotypes (p = 0.02). Lupus nephritis patients had a significantly higher frequency of DD versus DI and II genotypes compared with lupus patients without nephritis (Fisher's exact test, p = 0.025) and controls ( (2) =8.74, p = 0.003). SLE patients with vasculopathy had a significantly higher frequency of DD versus DI/II genotypes compared with SLE patients without vasculopathy (Fisher's exact test, p = 0.04) and controls ( (2 )= 9.84 and p = 0.002). Mean serum ACE level was significantly higher in the lupus nephritis and SLE patients with vasculopathy compared with controls (p = 0.008, p = 0.001, respectively). Significant positive correlations were found between serum ACE level and serum creatinine and 24 h proteinuria (p = 0.03, 0.009, respectively). SLE patients with DD genotype had a statistically significant higher mean SLEDAI score than those with (DI/II) genotypes (p = 0.02). Significant positive correlation was found between serum ACE levels and SLEDAI scores (p = 0.04). CONCLUSION: ACE genotype and subsequently serum ACE level could be associated with the disease activity of Egyptian SLE patients; in addition, ACE deletion polymorphism might be used as one of the predictive factors for the activity of SLE. Further studies on a larger number of patients should be done to determine the exact prevalence of ACE gene polymorphism among Egyptian SLE patients.

21976404

[]

21879313

[ "Genotype", "rs8099917", " ", "near", "the", "IL28B", "gene", "and", "amino", "acid", "substitution", "at", "position", "70", "in", "the", "core", "region", "of", "the", "hepatitis", "C", "virus", "are", "determinants", "of", "serum", "apolipoprotein", "B-100"...

[ 0, 5, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Genotype rs8099917 near the IL28B gene and amino acid substitution at position 70 in the core region of the hepatitis C virus are determinants of serum apolipoprotein B-100 concentration in chronic hepatitis C.

21879313

[ "The", "life", "cycle", "of", "the", "hepatitis", "C", "virus", "(HCV)", "is", "closely", "related", "to", "host", "lipoprotein", "metabolism.", "Serum", "levels", "of", "lipid", "are", "associated", "with", "the", "response", "to", "pegylated", "interferon", ...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

The life cycle of the hepatitis C virus (HCV) is closely related to host lipoprotein metabolism. Serum levels of lipid are associated with the response to pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy, while single nucleotide polymorphisms (SNPs) around the human interleukin 28B (IL28B) gene locus and amino acid substitutions in the core region of the HCV have been reported to affect the efficacy of PEG-IFN/RBV therapy in chronic hepatitis with HCV genotype 1b infection. The aim of this study was to elucidate the relationship between serum lipid and factors that are able to predict the efficacy of PEG-IFN/RB therapy, with specific focus on apolipoprotein B-100 (apoB-100) in 148 subjects with chronic HCV G1b infection. Our results demonstrated that both the aa 70 substitution in the core region of the HCV and the rs8099917 SNP located proximal to the IL28B were independent factors in determining serum apoB-100 and low-density lipoprotein (LDL) cholesterol levels. A significant association was noted between higher levels of apoB-100 (P = 1.1 10(-3)) and LDL cholesterol (P = 0.02) and the subjects having Arg70. A significant association was also observed between subjects carrying the rs8099917 TT responder genotype and higher levels of apoB-100 (P = 6.4 10(-3)) and LDL cholesterol (P = 4.2 10(-3)). Our results suggest that apoB-100 and LDL cholesterol are markers of impaired cellular lipoprotein pathways and/or host endogenous interferon response to HCV in chronic HCV infection. In particular, serum apoB-100 concentration might be an informative marker for judging changes in HCV-associated intracellular lipoprotein metabolism in patients carrying the rs8099917 responder genotype.

21879313

[]

20854438

[ "SLURP1", "mutation-impaired", "T-cell", "activation", "in", "a", "family", "with", "mal", "de", "Meleda." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

SLURP1 mutation-impaired T-cell activation in a family with mal de Meleda.

20854438

[ "BACKGROUND:", "Mal", "de", "Meleda", "(MDM)", "is", "palmoplantar", "erythrokeratoderma", "with", "an", "autosomal", "recessive", "inheritance", "and", "is", "caused", "by", "a", "mutation", "in", "the", "gene", "encoding", "SLURP-1", "(lymphocyte", "antigen", "6...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

BACKGROUND: Mal de Meleda (MDM) is palmoplantar erythrokeratoderma with an autosomal recessive inheritance and is caused by a mutation in the gene encoding SLURP-1 (lymphocyte antigen 6/urokinase-type plasminogen activator receptor related protein-1). SLURP-1 is an allosteric agonist to the nicotinic acetylcholine receptor (nAchR) and it regulates epidermal homeostasis. In addition, murine studies have shown that nAchR signalling is important for the regulation of T-cell function. Among the family members, patients with the homozygous SLURP1 (previously known as ARS component B) mutation are prone to melanoma and viral infection, which might link to defective T-cell function as well as a derangement of epidermal homeostasis. OBJECTIVES: To investigate the association of the SLURP1 gene mutation with T-cell activation in a Taiwanese family with MDM. To test that SLURP-1 is essential for T-cell activation. METHODS: Human peripheral blood mononuclear cells (PBMCs) were isolated from a Taiwanese MDM family bearing the G to A substitution in nucleotide 256 in the SLURP1 gene, corresponding to a glycine to arginine substitution at amino acid 86 ( G86R ) in the SLURP-1 protein. PBMCs from homozygotes and wild-type controls were stimulated with anti-CD3/anti-CD28 antibodies and the level of T-cell activation was determined by the stimulation index. RESULTS: PBMCs with the heterozygous and homozygous SLURP-1 G86R mutation had defective T-cell activation. This was restored by the addition of 0 5 ug mL(-1) recombinant human SLURP-1 protein. CONCLUSIONS: Patients with MDM with the homozygous SLURP-1 G86R mutation may have an impaired T-cell activation. The presence of wild-type SLURP-1 is essential for normal T-cell activation.

20854438

[]

20728296

[ "Interstitial", "deletion", "of", "13q14.13-q32.3", "presenting", "with", "Arima", "syndrome", "and", "bilateral", "retinoblastoma." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Interstitial deletion of 13q14.13-q32.3 presenting with Arima syndrome and bilateral retinoblastoma.

20728296

[ "A", "patient", "with", "a", "large", "deletion", "of", "the", "distal", "part", "of", "the", "long", "arm", "of", "chromosome", "13", "showed", "severe", "psychomotor", "retardation,", "a", "characteristic", "face,", "nystagmus,", "retinopathy,", "cystic", "kid...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

A patient with a large deletion of the distal part of the long arm of chromosome 13 showed severe psychomotor retardation, a characteristic face, nystagmus, retinopathy, cystic kidney disease, and brain malformation with molar tooth sign and cerebellar vermis hypoplasia, a phenotype typical of Arima syndrome. This patient also had bilateral retinoblastoma. Fluorescent in situ hybridization and single-nucleotide-polymorphism genotyping microarray demonstrated an interstitial deletion of 54 Mbp, ranging from 13q14.13 to 13q32.3 and involving the RB1 gene. This patient is the first case of Arima syndrome, or a Joubert syndrome-related disorder, that showed linkage to chromosome 13q.

20728296

[]

20887110

[ "Impact", "of", "5,10-methylenetetrahydrofolate", "reductase", "gene", "polymorphism", "on", "neural", "tube", "defects." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Impact of 5,10-methylenetetrahydrofolate reductase gene polymorphism on neural tube defects.

20887110

[ "OBJECT:", "Neural", "tube", "defects", "(NTDs)", "are", "among", "the", "most", "common", "congenital", "malformations", "worldwide.", "Their", "etiology", "and", "exact", "mechanisms", "of", "development", "are", "incompletely", "understood.", "Many", "enzymes", "...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0...

OBJECT: Neural tube defects (NTDs) are among the most common congenital malformations worldwide. Their etiology and exact mechanisms of development are incompletely understood. Many enzymes involved in folate metabolism and the genes encoding these enzymes have been studied as candidates in their etiology. A mutation in the methylenetetrahydrofolate reductase (MTHFR) gene--a C-->T transition at nucleotide 677 --is one among them. The mutation results in substitution of alanine by valine at a functionally important site in the enzyme. It has been shown to be a risk factor for development of NTDs in certain populations. The present study was conducted to evaluate the role of MTHFR 677 C-->T mutation as a risk factor for NTD in the South Indian population and to determine the relative importance of the genotypes in the affected child and its mother. METHODS: Blood samples were collected from the test and the control groups. The test group consisted of children with NTDs and their mothers, while the control group consisted of apparently healthy controls. MTHFR C677T polymorphism in the 3 groups was determined by polymerase chain reaction and restriction fragment length polymorphism studies. Comparison of polymorphism in the 3 groups was using the chi-square test. RESULTS: There was a significant difference in the prevalence of MTHFR 677 C-->T mutation among the 3 groups (p = 0.002). The risk conferred by the TT genotype in the child was statistically significant (OR 12.625, 95% CI 1.430-111.465). In the mothers, however, although there was an increased prevalence of the mutation compared with the control individuals, the difference was not statistically significant (p = 0.152). CONCLUSIONS: The MTHFR 677TT genotype is considered to be a definite risk factor for development of NTDs. It is the TT genotype status of the developing embryo, rather than the TT genotype status of its mother, that is the critical genetic determinant of MTHFR-related NTD risk.

20887110

[]

20602574

[ "Bikunin", "and", "a1-microglobulin/bikunin", "precursor", "(AMBP)", "gene", "mutational", "screening", "in", "patients", "with", "kidney", "stones:", "a", "case-control", "study." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Bikunin and a1-microglobulin/bikunin precursor (AMBP) gene mutational screening in patients with kidney stones: a case-control study.

20602574

[ "OBJECTIVE:", "Bikunin", "is", "an", "inhibitor", "of", "kidney", "stone", "formation", "synthesized", "in", "the", "liver", "together", "with", "a(1)-microglobulin", "from", "the", "a(1)-microglobulin/bikunin", "precursor", "(AMBP)", "gene.", "The", "aim", "of", "t...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

OBJECTIVE: Bikunin is an inhibitor of kidney stone formation synthesized in the liver together with a(1)-microglobulin from the a(1)-microglobulin/bikunin precursor (AMBP) gene. The aim of this study was to investigate the possible association between bikunin/AMBP gene polymorphisms and urinary stone formation. MATERIAL AND METHODS: To analyse the DNA, blood samples were taken from 75 kidney stone formers who had a familial stone history, 35 sporadic stone formers and 101 healthy individuals. Four exons of bikunin gene and five parts of the promoter region of the AMBP gene were screened using single-strand conformation polymorphism and nucleotide sequence analysis. RESULTS: The Init-2 region of the promoter of AMBP gene had polymorphisms at positions -218 and -189 nt giving three different genotypes having 1,3, 2,4 and 1,2,3,4 alleles with frequencies of 17.06%, 60.19% and 22.75%, respectively, in all groups. Therefore, the Init-2 region appears to be polymorphic. As a result, the 1,3 allele has -218G and -189T complying with the reference database sequence, the 2,4 allele has -218G and T-189C substitution and the allele 1,2,3,4 genotype has substitutions at positions G-218C and T-189C . CONCLUSIONS: There were no significant differences in allele distribution between patients and controls. These common alleles exist in the Turkish population independent of stone formation. These results are the first to demonstrate the existence of bikunin and AMBP promoter polymorphism. Although the Init-2 region of the AMBP gene is the binding site for various transcription factors, the results showed no association between these observed genotypes and stone-forming phenotypes.

20602574

[]

21080147

[ "Novel", "CRELD1", "gene", "mutations", "in", "patients", "with", "atrioventricular", "septal", "defect." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Novel CRELD1 gene mutations in patients with atrioventricular septal defect.

21080147

[ "BACKGROUND:", "Atrioventricular", "septal", "defects", "(AVSDs)", "occur", "as", "clinical", "defects", "of", "several", "different", "syndromes,", "as", "autosomal", "dominant", "defects,", "and", "as", "sporadically", "occurring", "malformations.", "Consequently,", "...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

BACKGROUND: Atrioventricular septal defects (AVSDs) occur as clinical defects of several different syndromes, as autosomal dominant defects, and as sporadically occurring malformations. Consequently, there is genetic heterogeneity, but until recently, little is known about the genes involving in the pathogenesis of AVSD. CRELD1 gene, a novel cell adhesion molecule, is a candidate gene for AVSD. METHODS: This study included 133 patients with AVSD and 200 healthy controls. Peripheral blood samples were collected and genomic DNA was extracted from the leukocytes. CRELD1 was amplified by polymerase chain reaction (PCR) with specific primers. The sequences of PCR products were compared between the patients and controls. RESULTS: In a patient, a C-to-G transition was identified at nucleotide 857 in exon 8 that resulted in a substitution of alanine for proline at amino acid 286 in the first calcium-binding EGF domain. This patient had an isolated partial AVSD and the mutation was inherited from her mother. Another mutation was detected in a patient with a partial AVSD and evidence of Down syndrome. The heterozygous c.973G>A transition in exon 9 resulted in a substitution of lysine for glutamic acid at amino acid 325 ( E325K ) in the second calcium-binding EGF domain. CONCLUSIONS: Two novel CRELD1 mutations were identified in the calcium-binding EGF domain in patients with AVSD. CRELD1 is likely to be an AVSD-susceptibility gene and CRELD1 mutations may increase the risk of developing a heart defect rather than being a direct causative mutation.

21080147

[]

20708777

[ "Association", "of", "DNA", "polymorphisms", "within", "the", "CYP11B2/CYP11B1", "locus", "and", "postoperative", "hypertension", "risk", "in", "the", "patients", "with", "aldosterone-producing", "adenomas." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Association of DNA polymorphisms within the CYP11B2/CYP11B1 locus and postoperative hypertension risk in the patients with aldosterone-producing adenomas.

20708777

[ "OBJECTIVES:", "Hypertension", "often", "persists", "after", "adrenalectomy", "for", "primary", "aldosteronism.", "Traditional", "factors", "associated", "with", "postoperative", "hypertension", "were", "evaluated,", "but", "whether", "genetic", "determinants", "were", "i...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

OBJECTIVES: Hypertension often persists after adrenalectomy for primary aldosteronism. Traditional factors associated with postoperative hypertension were evaluated, but whether genetic determinants were involved remains poorly understood. The aim of this study was to investigate the association of DNA polymorphisms within steroid synthesis genes (CYP11B2, CYP11B1) and the postoperative resolution of hypertension in Chinese patients undergoing adrenalectomy for aldosterone-producing adenomas (APA). METHODS: Ninety-three patients with APA were assessed for postoperative resolution of hypertension. All patients were genotyped for rs1799998 ( C-344 T ), intron 2 conversion, rs4539 ( A2718G ) within CYP11B2 and rs6410 ( G22 5A ), rs6387 ( A2803G ) within CYP11B1. The associations between CYPB11B2/CYP11B1 polymorphisms and persistent postoperative hypertension were assessed by multivariate analysis. RESULTS: CYP11B2-CYP11B1 haplotype was associated with persistent postoperative hypertension in Chinese patients undergoing adrenalectomy with APA (P = .006). Specifically, the rs4539 (AA) polymorphism was associated with persistent postoperative hypertension (P = .002). Multivariate logistic regression revealed the common haplotypes H1 (AGACT), H2 (AGAWT), and H3 (AGAWC) were associated with the persistent postoperative hypertension (P = .01, 0.03, 0.005 after Bonferroni correction). Additional predictors of persistent postoperative hypertension included duration of hypertension (P <.0005), family history of hypertension (P = .001), and elevated systolic blood pressure (P = .015). CONCLUSIONS: The rs4539 (AA), H1, H2, and H3 are genetic predictors for postoperative persistence of hypertension for Chinese patients treated by adrenalectomy with APA. DNA polymorphisms at CYP11B2/B1 locus may confer susceptibility to postoperative hypertension of patients with APA.

20708777

[]

21059483

[ "The", "GALT", "rush:", "high", "carrier", "frequency", "of", "an", "unusual", "deletion", "mutation", "of", "the", "GALT", "gene", "in", "the", "Ashkenazi", "population." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

The GALT rush: high carrier frequency of an unusual deletion mutation of the GALT gene in the Ashkenazi population.

21059483

[ "Classic", "galactosemia", "is", "an", "autosomal", "recessive", "disorder", "of", "galactose", "metabolism", "manifesting", "in", "the", "first", "weeks", "of", "life", "following", "exposure", "to", "a", "milk-based", "diet.", "Despite", "the", "benefit", "of", ...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

Classic galactosemia is an autosomal recessive disorder of galactose metabolism manifesting in the first weeks of life following exposure to a milk-based diet. Despite the benefit of avoidance of lactose, many patients suffer from long-term complications including neurological deficits and ovarian failure. To date, over 230 mutations have been described in the GALT gene resulting in galactosemia. Recently, an unusual mutation was characterized causing a 5.5 kb deletion, with a relatively high carrier rate in subjects of Ashkenazi Jewish (AJ) descent. The aim of this study was to estimate the carrier frequency of this mutation in the AJ population in Israel. For this purpose we developed a high-throughput methodology to genotype both normal and deleted alleles using a chip-based matrix-assisted laser desorption-time-of-flight (MALDI-TOF) mass spectrometer and Multiplex PCR. DNA samples of 760 anonymous AJ subjects were submitted for analysis, subsequently detecting six individuals heterozygous for the GALT deletion mutation, giving a carrier frequency of 1 in 127 (0.79%). Based on these results, we suggest that the method described here provides a basis for genetic screening and prenatal counseling and can potentially reduce the morbidity and mortality associated with delayed diagnosis of galactosemia in this patient population.

21059483

[]

21103668

[ "Characterisation", "of", "two", "novel", "large", "F8", "deletions", "in", "patients", "with", "severe", "haemophilia", "A", "and", "factor", "VIII", "inhibitors." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Characterisation of two novel large F8 deletions in patients with severe haemophilia A and factor VIII inhibitors.

21103668

[ "Large", "deletions", "are", "found", "in", "approximately", "5%", "of", "patients", "with", "severe", "haemophilia", "A,", "but", "only", "a", "few", "deletion", "breakpoints", "have", "been", "characterised", "precisely", "so", "far.", "In", "this", "study", ...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

Large deletions are found in approximately 5% of patients with severe haemophilia A, but only a few deletion breakpoints have been characterised precisely so far. In this study we characterised the deletion breakpoints of two patients with severe haemophilia A, large deletions and factor VIII (FVIII) inhibitors, and subsequently established deletion-specific assays for the identification of carriers. Patient 1 had a deletion of 37,410 bp comprising exon 1 and the F8 promoter region, and a 5 bp homology (GGGCC) is present at the chromosomal fusion site. In patient 2, a deletion of 22,230 bp including parts of intron 25, exon 26 and 3'-UTR was identified. No homologous repetitive elements were found at the breakpoints. However, both breakpoints were located within long terminal repeats of endogenous retroviruses and the DNA motif TTTAAA - known to be able to bend DNA molecules - was identified at the centromeric breakpoint. By deletion-specific PCR experiments we were able to identify a heterozygous state in mother 2 (carrier) while mother 1 presented only with wild-type alleles (non-carrier). Both deletions are most likely created by DNA double strand breaks and subsequent DNA repair by the non-homologous end joining DNA repair pathway (NHEJ). The exact identification of the deletion breakpoints provides a reliable diagnostic tool for carrier identification in affected families by means of a deletion-specific PCR.

21103668

[]

20682662

[ "Lack", "of", "association", "of", "C-C", "chemokine", "receptor", "5", "/\\32", "deletion", "status", "with", "rheumatoid", "arthritis,", "systemic", "lupus", "erythematosus,", "lupus", "nephritis,", "and", "disease", "severity." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

Lack of association of C-C chemokine receptor 5 /\32 deletion status with rheumatoid arthritis, systemic lupus erythematosus, lupus nephritis, and disease severity.

20682662

[ "OBJECTIVE:", "C-C", "chemokine", "receptor", "5", "(CCR5)", "plays", "an", "important", "role", "in", "inflammation.", "A", "32", "base-pair", "(/\\32)", "deletion", "in", "the", "CCR5", "gene", "leads", "to", "a", "nonfunctional", "receptor.", "This", "deletio...

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0...

OBJECTIVE: C-C chemokine receptor 5 (CCR5) plays an important role in inflammation. A 32 base-pair (/\32) deletion in the CCR5 gene leads to a nonfunctional receptor. This deletion has been reported to have a protective effect on the development and progression of several autoimmune diseases. We investigated whether the /\32 deletion is associated with disease susceptibility in a population of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and lupus nephritis (LN); and whether it is associated with disease severity. METHODS: DNA samples from 405 RA patients, 97 SLE patients, 113 LN patients, and 431 healthy controls were genotyped for the CCR5 /\32 deletion. Differences in genotype frequencies were tested between patients and controls. Association of genotypes with disease severity was analyzed. RESULTS: Genotype frequencies of each group were in Hardy-Weinberg equilibrium. The genotype frequencies of patients did not differ significantly from controls (CCR5//\32, /\32//\32: RA 18.3% and 1.2%, respectively; SLE 17.5% and 2.1%; LN 13.3% and 1.8%; controls 20.0% and 2.8%). However, there was a trend for lower /\32 deletion allele frequency in LN patients compared to controls (p = 0.08). There was no significant association between the CCR5 status and disease severity in RA, SLE, or LN. CONCLUSION: Although an association with LN cannot be excluded, the CCR5 /\32 deletion does not seem to be a disease susceptibility genotype for RA, SLE, or LN. No significant effect of the /\32 deletion on disease severity was demonstrated.

20682662

[]

20806042

[ "A", "novel", "mutation", "in", "GJA8", "causing", "congenital", "cataract-microcornea", "syndrome", "in", "a", "Chinese", "pedigree." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

A novel mutation in GJA8 causing congenital cataract-microcornea syndrome in a Chinese pedigree.