bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of two supernumerary marker chromosomes in a patient with signs of Klinefelter syndrome, mild facial anomalies, and severe speech delay*
Authors: Weimer Jörg , Metzke‐Heidemann Simone , Plendl Hansjörg , Caliebe Almuth , Grunewald Regina , Õunap Katrin , Tammur Pille , Jonat Walter , Bartsch Oliver , Siebert Reiner , Arnold Norbert 
Published: February 2006

AbstractA boy with signs of Klinefelter syndrome, mild facial dysmorphic features, and severely retarded speech development displayed a female karyotype with mosaicism for two marker chromosomes 48,XX,+mar1,+mar2[68]/47,XX,+mar1[19]/47,XX,+mar2[6]/46,XX[8]. Using chromosomal microdissection, locus‐specific fluorescence in situ hybridization (FISH), and PCR with several Y‐chromosome markers, the larger supernumerary marker chromosome (SMC) was characterized as a ring Y‐chromosome. Detection of the SRY‐region explained the male phenotype. The smaller second marker chromosome contained the pericentromeric region of chromosome 8. We suggest that the co‐occurrence of a partial Y‐chromosome and partial trisomy 8 explain the severe speech delay and the facial dysmorphic features. © 2006 Wiley‐Liss, Inc.
A truncating mutation in the IL1RAPL1 gene is responsible for X‐linked mental retardation in the MRX21 family
Authors: Tabolacci Elisabetta , Pomponi M. Grazia , Pietrobono Roberta , Terracciano Alessandra , Chiurazzi Pietro , Neri Giovanni 
Published: February 2006

AbstractX‐linked mental retardation (XLMR) is a genetically heterogeneous condition, due to mutations in at least 50 genes, involved in functioning of the central nervous system and located on the X chromosome. Nonspecific XLMR (MRX) is characterized essentially by mental retardation transmitted by X‐linked inheritance. More than 80 extended MRX pedigrees have been reported to date, which have been distinguished exclusively by physical position of the corresponding gene on the X chromosome, established by linkage analysis. One such family, MRX21, which was described by us in 1993 and localized to Xp11.4‐pter, has now been reanalyzed with additional markers and after one more affected individual had became available. This extra information allowed a significant reduction of the linkage interval and, eventually, identification of the mutant gene. A stop mutation in exon 10 of the IL1RAPL1 gene (in Xp21) was found in the four affected males and in obligate carriers, allowing conclusive counseling of other family members of uncertain carrier status. The W487X mutation results in the production of a truncated IL1RAPL protein, comprised of the extracellular Ig‐like domain and transmembrane tract, but lacking the last 210 aminoacids of the cytoplasmic domain. MRX21 is the first extended MRX family with a point mutation in IL1RAPL1 and the second with a stop mutation, which had been previously found only in a small family. Our report confirms the role of the IL1RAPL1 gene in causing nonspecific mental retardation in males and underlines the importance of detailed linkage analysis before candidate gene mutational screening. © 2006 Wiley‐Liss, Inc.
Speech and language impairment and oromotor dyspraxia due to deletion of 7q31 that involves FOXP2
Authors: Zeesman Susan , Nowaczyk Małgorzata J.M. , Teshima Ikuko , Roberts Wendy , Cardy Janis Oram , Brian Jessica , Senman Lili , Feuk Lars , Osborne Lucy R. , Scherer Stephen W. 
Published: February 2006

AbstractWe report detailed clinical, cytogenetic, and molecular findings in a girl with a deletion of chromosome 7q31‐q32. This child has a severe communication disorder with evidence of oromotor dyspraxia, dysmorphic features, and mild developmental delay. She is unable to cough, sneeze, or laugh spontaneously. Her deletion is on the paternally inherited chromosome and includes the FOXP2 gene, which has recently been associated with speech and language impairment and a similar form of oromotor dyspraxia in at least three other published cases. We hypothesize that our patient's communication disorder and oromotor deficiency are due to haploinsufficiency for FOXP2 and that her dysmorphism and developmental delay are a consequence of the absence of the other genes involved in the microdeletion. We propose that this patient, together with others reported in the literature, may define a new contiguous gene deletion syndrome encompassing the 7q31‐FOXP2 region. Cytogenetic and molecular analysis of this region should be considered for other individuals displaying similar characteristics. © 2006 Wiley‐Liss, Inc.
Variable contribution of the MTHFR C677T polymorphism to non‐syndromic cleft lip and palate risk in China
Authors: Zhu JiangHui , Ren AiGuo , Hao Ling , Pei LiJun , Liu JianMeng , Zhu HuiPing , Li Song , Finnell Richard H. , Li Zhu 
Published: February 2006

AbstractNon‐syndromic cleft lip with or without cleft palate (nsCL/P) is one of the most common craniofacial malformations among newborn infants. It has been demonstrated that periconceptional folic acid supplementation may reduce the occurrence of offspring with clefts, particularly in the North China; however, the mechanism remains unknown. Our study of a thermolabile polymorphism (C677T) of methylenetetrahydrofolate reductase (MTHFR) gene in 170 Chinese case‐parent triads revealed a moderate association between this MTHFR polymorphism and nsCL/P in a population from North China, but not in a population from South China. Moreover, the study revealed that the heterozygous parents in the North were about twice as likely to transmit the high‐risk T allele to affected cases, as that observed in the South (OR = 2.24, 95% CI: 1.08–4.65). Thus, the MTHFR polymorphism is a significant risk factor for nsCL/P in this Northern Chinese population. Our study suggested possible genetic heterogeneity in the development of nsCL/P among Northern and Southern populations in China. © 2006 Wiley‐Liss, Inc.
Mitochondrial dysfunction in Brooks–Wisniewski–Brown syndrome
Authors: Morava Eva , Rodenburg Richard , Hol Frans , De Meirleir Linda , Seneca Sara , Busch Rebekka , van den Heuvel Lambert , Smeitink Jan 
Published: February 2006

AbstractBrooks, Wisniewski, and Brown described a familial presentation of severe developmental retardation, speech delay, static encephalopathy with atrophic hydrocephalus, microcephaly, progressive spastic diplegia, a characteristic facial appearance, optic atrophy, and growth retardation associated with hypoplastic corpus callosum in one of the patients. The authors postulated a distinct X‐linked mental retardation syndrome. Later on a similar phenotype was observed in three male siblings with an early lethal outcome. Here we describe three patients with several overlapping features and a progressive neurological picture presenting with a significantly compromised mitochondrial oxidative phosphorylation measured in a fresh muscle biopsy. Neurological deterioration is a commonly observed feature in mitochondrial disorders. Based on the unique combination of the clinical symptoms, we suggest that our patients have the Brooks–Wisniewski–Brown syndrome. © 2006 Wiley‐Liss, Inc.
Interstitial 2.2 Mb deletion at 9q34 in a patient with mental retardation but without classical features of the 9q subtelomeric deletion syndrome
Authors: Kleefstra Tjitske , Koolen David A. , Nillesen Willy M. , de Leeuw Nicole , Hamel Ben C.J. , Veltman Joris A. , Sistermans Erik A. , van Bokhoven Hans , van Ravenswaay Conny , de Vries Bert B.A. 
Published: February 2006

AbstractIn a female patient with mild mental retardation an interstitial subtelomeric 9q34.3 deletion was identified by a multiplex ligation‐dependent probe amplification (MLPA) based screen for subtelomeric abnormalities. Further characterization of the deletion by high‐resolution tiling path array‐based comparative genomic hybridization (array CGH) revealed a size of 2.2 Mb. The woman lacked the typical 9qter deletion phenotype characteristics, which is inline with the finding that both Eu‐HMTase1 (EHMT) genes were present. However, she presented with mild mental retardation, some mild facial dysmorphisms and aplasia cutis. This is another example of an interstitial subtelomeric deletion, which underscores that further characterizing the precise nature of the deletion is of clinical importance. Moreover, it confirms the importance of the Eu‐HMTase1 gene as the major causative factor of the classical 9qter syndrome phenotype. © 2006 Wiley‐Liss, Inc.
Systematic search for single nucleotide polymorphisms in a lymphoid tyrosine phosphatase gene (PTPN22): Association between a promoter polymorphism and type 1 diabetes in Asian populations
Authors: Kawasaki Eiji , Awata Takuya , Ikegami Hiroshi , Kobayashi Tetsuro , Maruyama Taro , Nakanishi Koji , Shimada Akira , Uga Mho , Kurihara Susumu , Kawabata Yumiko , Tanaka Shoichiro , Kanazawa Yasuhiko , Lee Inkyu , Eguchi Katsumi ,   Japanese Study Group on Type 1 Diabetes Genetics
Published: February 2006

AbstractThe protein tyrosine phosphatase, nonreceptor 22 gene (PTPN22) maps to human chromosome 1p13.3‐p13.1 and encodes an important negative regulator of T‐cell activation, lymphoid‐specific phosphatase (Lyp). Recently, the minor allele of a single‐nucleotide polymorphism (SNP) at nucleotide position 1858 (rs2476601, +1858C > T) was found to be associated with type 1 diabetes. However, the degree of the association is variable among ethnic populations, suggesting the presence of other disease‐associated variants in PTPN22. To examine this possibility, we carried out a systemic search for PTPN22 using direct sequencing of PCR‐amplified products in the Japanese population. Association and linkage studies were also conducted in 1,690 Japanese samples, 180 Korean samples, and 472 Caucasian samples from 95 nuclear families. We identified five novel SNPs, but not the +1858C > T SNP. Of these two frequent SNPs, −1123G > C, and +2740C > T were in strong linkage disequilibrium (LD), and the −1123G > C promoter SNP was associated with acute‐onset but not slow‐onset type 1 diabetes in the Japanese population (odds ratio [OR] = 1.42, 95% CI = 1.07–1.89, P = 0.015). This association was observed also in Korean patients with type 1 diabetes (Mantel–Haenszel χ2 = 6.543, P = 0.0105, combined OR = 1.41 95% CI = 1.09–1.82). Furthermore, the affected family‐based control (AFBAC) association test and the transmission disequilibrium analysis of multiplex families of European descent from the British Diabetes Association (BDA) Warren Repository indicated that the association was stronger in −1123G > C compared to +1858C > T. In conclusion, the type 1 diabetes association with PTPN22 is confirmed, but it cannot be attributed solely to the +1858C > T variant. The promoter −1123G > C SNP is a more likely causative variant in PTPN22. © 2006 Wiley‐Liss, Inc.
A novel mutation in the DNA‐binding domain of MAF at 16q23.1 associated with autosomal dominant “cerulean cataract” in an Indian family
Authors: Vanita Vanita , Singh Daljit , Robinson Peter N. , Sperling Karl , Singh Jai Rup 
Published: February 2006

AbstractCongenital cataract, a clinically and genetically highly heterogeneous eye disorder, is one of the significant causes of visual impairment or blindness in children. It is frequently inherited as an autosomal dominant trait. We investigated a three‐generation family of Indian origin with 12 members affected with cerulean cataract. Linkage analysis was carried out in this family using more than 100 microsatellite markers for the known cataract candidate gene loci. A positive two‐point lod score of 3.9 at θ = 0.000, indicative of linkage, was obtained with three microsatellite markers for chromosome 16. Multipoint and haplotype analysis narrowed the cataract locus to a 15.3 cM region between markers D16S518 and D16S511 that corresponds to the region 16q23.1. Direct sequencing of the candidate gene MAF, which lies in the critical linked region, revealed a novel heterozygous missense mutation in the basic region (BR) of the DNA‐binding domain. This sequence change was considered pathogenic as it segregated in all affected family members, neither seen in unaffected family members nor in 106 unrelated controls. The mutation also results in substitution of highly conserved lysine 297 by arginine (K297R) that affects a residue that forms a part of a predicted DNA‐interaction region of the protein. The association of microcornea with congenital cataract in some affected individuals further underlines the role of the MAF transcription factor in lens and anterior ocular development. Our findings expand the mutation spectrum of MAF in association with congenital cataract and highlight the genetic and phenotypic heterogeneity of congenital cataract. © 2006 Wiley‐Liss, Inc.
Mosaic trisomy 6 and maternal uniparental disomy 6 in a 23‐week gestation fetus with atrioventricular septal defect
Authors: Cockwell Annette E. , Baker Samantha J. , Connarty Margaret , Moore Isabella E. , Crolla John A. 
Published: February 2006

AbstractTrisomy 6 is seen in early miscarriages in association with an intact, empty amniotic sac or as a pseudomosaic in amniotic fluid cultures. We report the finding of mosaic trisomy 6 in a 23‐week‐gestation pregnancy terminated because of intrauterine death. The post‐mortem showed a well formed macerated male fetus with an atrioventricular septal defect and an exomphalos. By conventional cytogenetics, trisomy 6 was found in 12 out of 25 (48%) fibroblast colonies from fetal skin and 21 out of 32 (66%) colonies derived from amnion, while the remaining metaphases showed an apparently normal male karyotype. Molecular genetic studies on DNA from uncultured fetal skin and cord samples using polymorphic microsatellite repeat sequences showed no evidence of trisomy 6, but demonstrated that both chromosome 6 homologs were of maternal origin consistent with maternal uniparental disomy (UPD). © 2006 Wiley‐Liss, Inc.
Ring chromosome 4 and Wolf–Hirschhorn syndrome (WHS) in a child with multiple anomalies
Authors: Balcı Sevim , Engiz Özlem , Aktaş Dilek , Vargel Ibrahim , Beksaç M.S. , Mrasek Kristin , Vermeesch Joris , Liehr Thomas 
Published: February 2006

AbstractWe report on a 16‐month‐old male patient with ring chromosome 4 and deletion of Wolf–Hirschhorn syndrome (WHS) region with multiple congenital anomalies including unilateral cleft lip and palate, iris coloboma, microcephaly, midgut malrotation, hypospadias, and double urethral orifices. Peripheral chromosome analysis of the patient showed 46,XY,r(4)(p16.3q35) de novo. Multicolor fluorescence in situ hybridization (FISH) study was also performed and according to multicolor banding (MCB) a r(4)(::p16.3 → q34.3 ∼ 35.1::) was found in all metaphases. Subtelomeric 4p region, subtelomeric 4q region, as well as, Wolf–Hirschhorn critical region were deleted in ring chromosome 4. Genomic microarray analysis was also performed to delineate the size of deletion. Cranial magnetic resonance imaging (MRI) showed hypoplastic corpus callosum, delayed myelinization, and frontal and occipital lobe atrophies. Both maternal and paternal chromosomal analyses were normal. We compare the phenotypic appearance of our patient with the previously reported 16 cases of ring chromosome 4 in the medical literature. © 2006 Wiley‐Liss, Inc.
A 9‐year‐old male with a duplication of chromosome 3p25.3p26.2: Clinical report and gene expression analysis
Authors: Bittel Douglas C. , Kibiryeva Nataliya , Dasouki Majed , Knoll Joan H.M. , Butler Merlin G. 
Published: February 2006

AbstractWe describe a 9‐year‐old male referred for genetic evaluation for Prader‐Willi syndrome (PWS). PWS is the most common genetically defined cause of life‐threatening obesity and results from a functional loss of paternally expressed genes from the chromosome 15q11‐q13 region. The patient presented with pervasive developmental disorder, delayed speech, and rapid onset of obesity at age 4 years, all features similar to PWS. However, chromosome 15q11‐q13 methylation testing and fragile X studies were normal. GTG‐banding and fluorescence in situ hybridization (FISH) with whole chromosome 3 paint probe (WCP3) and a chromosome 3p subtelomeric probe suggested a duplication of 3p25.3p26.2, a finding supported by comparative genomic hybridization (CGH). This region of chromosome 3p contains genes which contribute to obesity and behavioral problems, most notably, ghrelin (GHRL), an oxytocin receptor (OXTR), solute carrier family six members (gamma‐aminobutyric acid (GABA) neurotransmitter transporters, SLC6A1 and SLC6A11), and peroxisome proliferator‐activated receptor gamma (PPARG). To characterize these obesity and behavior related genes in our subject, we performed quantitative RT‐PCR and compared expression levels with similarly aged male subjects (four non‐obese males, four obese males, and four PWS males—two with 15q11‐q13 deletions and two with maternal disomy 15). Our studies suggest increased expression of several genes in the 3p duplication region, including GHRL and PPARG, which may contribute to the phenotypic features in our 3p duplication subject. © 2006 Wiley‐Liss, Inc.
A nonsense mutation of PEPD in four Amish children with prolidase deficiency
Authors: Wang Heng , Kurien Biji T. , Lundgren David , Patel Nisha C. , Kaufman K. M. , Miller David L. , Porter Andrew C. , D'Souza Anil , Nye Leah , Tumbush John , Hupertz Vera , Kerr Douglas S. , Kurono S. , Matsumoto H. , Scofield R. Hal 
Published: February 2006

AbstractEncoded by the peptidase D (PEPD) gene located at 19q12‐q13.11, prolidase is a ubiquitous cytosolic enzyme that catalyzes hydrolysis of oligopeptides with a C‐terminal proline or hydroxyproline. We describe here four Amish children with a severe phenotype of prolidase deficiency in the Geauga settlements of Ohio as the first report of prolidase deficiency in the Amish population as well as in the United States. The patients presented with infection, hepatosplenomegaly, or thrombocytopenia, in contrast to most cases previously reported in the literature, presenting with skin ulcers. All four patients had typical facial features, classic skin ulcers, and multisystem involvement. Recurrent infections, asthma‐like chronic reactive airway disease, hyperimmunoglobulins, hepatosplenomegaly with mildly elevated aspartate transaminase (AST), anemia, and thrombocytopenia were common and massive imidodipeptiduria was universal. Prolidase activity in our patients is nearly undetectable. Direct sequencing of PCR‐amplified genomic DNA for all of the exons from the four patients revealed the same homozygous single nucleotide mutation c.793 T > C in exon 11, resulting in a premature stop‐codon at amino acid residue 265 (p.R265X). It is speculated that the severe phenotype in these patients might be associated with the type of the PEPD gene mutation. © 2006 Wiley‐Liss, Inc.
Molecular cytogenetic analysis of a familial interstitial deletion Xp22.2‐22.3 with a highly variable phenotype in female carriers
Authors: Chocholska Sylwia , Rossier Eva , Barbi Gotthold , Kehrer‐Sawatzki Hildegard 
Published: February 2006

AbstractWe describe a familial interstitial deletion of 7.7‐Mb involving Xp22.2‐22.3. The deletion was transmitted from an asymptomatic mother to her two children with severe developmental delay, no speech development and autistic behavior. Assessment of the deletion boundaries by FISH and PCR analyses indicated that the deletions encompasses 27 genes. Several of these genes are associated with known disorders, like KAL1 (Kallmann syndrome), steroid sulfatase (STS) (X‐linked ichtyosis), and arylsulfatase E (ARSE) (chondrodysplasia punctata). The deletion also includes all four VCX genes (VCX‐A, VCX‐B1, VCX‐B, and VCX‐C) and the neuroligin 4 (NLGN4) gene. VCX‐A deficiency has been shown previously to be associated with mental retardation and NLGN4 mutations lead to mental retardation in conjunction with autism. Functional deficiency of both MRX genes, VCX‐A and NLGN4, are most likely associated with the impaired cognitive development of the patients described here. The phenotype associated with the Xp deletion was highly variable in female carriers and might be attributed to unfavorable X inactivation. However, all the 27 genes included in the deleted interval escape X inactivation and are expressed at variable levels from the normal X chromosome. Thus, the overall X inactivation pattern and inter‐individual expression variability of the genes in distal Xp might be determinants of the phenotype associated with the deletion. © 2006 Wiley‐Liss, Inc.
Brain imaging evidence of preclinical Alzheimer's disease in normal aging
Authors: Jagust William , Gitcho Amy , Sun Felice , Kuczynski Beth , Mungas Dan , Haan Mary 
Published: February 2006

AbstractObjectiveThis study was designed to test the hypothesis that baseline glucose metabolism and medial temporal lobe brain volumes are predictive of cognitive decline in normal older people.MethodsWe performed positron emission tomography using [18F]fluorodeoxyglucose and structural magnetic resonance imaging at baseline in 60 cognitively normal community‐dwelling older subjects who were part of a longitudinal cohort study. Subjects were followed for a mean of 3.8 years, with approximately annual evaluation of global cognition (the Modified Mini‐Mental State Examination) and episodic memory (delayed recall). Baseline brain volumes and glucose metabolism were evaluated in relation to the rate of change in cognitive test scores.ResultsSix subjects developed incident dementia or cognitive impairment (converters). Baseline positron emission tomography scans showed regions in left and right angular gyrus, left mid‐temporal gyrus, and left middle frontal gyrus that predicted the rate of change on the Modified Mini‐Mental State Examination (p < 0.001). The left hemisphere temporal and parietal regions remained significant when converters were excluded. Both hippocampal (p = 0.03) and entorhinal cortical volumes (p = 0.01) predicted decline on delayed recall over time, and entorhinal cortical volumes remained significant when converters were excluded (p = 0.02). These brain volumes did not predict Modified Mini‐Mental State Examination decline.InterpretationThese results indicate that temporal and parietal glucose metabolism predict decline in global cognitive function, and medial temporal brain volumes predict memory decline in normal older people. The anatomical location of these findings suggests detection of preclinical Alzheimer's disease pathology. Ann Neurol 2006
Das Reaktivitäts‐Selektivitäts‐Prinzip: ein unzerstörbarer Mythos der organischen Chemie
Authors: Mayr Herbert , Ofial Armin R. 
Published: February 2006

AbstractDas Reaktivitäts‐Selektivitäts‐Prinzip (RSP), früher ein unumstrittener Lehrsatz der organischen Chemie, wurde in den 1970er Jahren ausgehöhlt und um 1980 mehr oder weniger aufgegeben. Obwohl nun seit mehr als 25 Jahren klar ist, dass abnehmende Selektivität als Folge zunehmender Reaktivität nur dann erwartet werden kann, wenn man sich auf die Diffusionsgrenze zu bewegt, lebt das RSP als intuitiv eingängige Regel weiter. Dieser Kurzaufsatz zeigt, warum es überhaupt nicht möglich sein kann, dass die Selektivität mit zunehmender Reaktivität generell abnimmt, und beleuchtet die Schwachstellen der theoretischen Grundlagen des RSP.
The Reactivity–Selectivity Principle: An Imperishable Myth in Organic Chemistry
Authors: Mayr Herbert , Ofial Armin R. 
Published: February 2006

AbstractThe reactivity–selectivity principle (RSP), once a tenet of organic chemistry, eroded during the 1970s and was more or less abandoned by 1980. Although it has been clear for more than 25 years that a decrease in selectivity with increasing reactivity can only be expected with certainty if diffusion control is approached, the RSP has survived as an intuitively appealing rule. This Minireview shows why selectivity cannot generally decrease with increasing reactivity and highlights the weaknesses of the theoretical foundations of the RSP.