GTF2I hemizygosity implicated in mental retardation in Williams syndrome: Genotype-phenotype analysis of five families with deletions in the Williams syndrome region Export

@article{citeulike:142710, abstract = {Most individuals with Williams syndrome (WS) have a 1.6 Mb deletion in chromosome 7q11.23 that encompasses the elastin (<I >ELN</I >) gene, while most families with autosomal dominant supravalvar aortic stenosis (SVAS) have point mutations in <I >ELN</I >. The overlap of the clinical phenotypes of the two conditions (cardiovascular disease and connective tissue abnormalities such as hernias) is due to the effect of haploinsufficiency of <I >ELN</I >. SVAS families often have affected individuals with some WS facial features, most commonly in infancy, suggesting that <I >ELN</I > plays a role in WS facial gestalt as well. To find other genes contributing to the WS phenotype, we studied five families with SVAS who have small deletions in the WS region. None of the families had mental retardation, but affected family members had the Williams Syndrome Cognitive Profile (WSCP). All families shared a deletion of <I >LIMK1</I >, which encodes a protein strongly expressed in the brain, supporting the hypothesis that <I >LIMK1</I > hemizygosity contributes to impairment in visuospatial constructive cognition. While the deletions from the families nearly spanned the WS region, none had a deletion of <I >FKBP6</I > or <I >GTF2I</I >, suggesting that the mental retardation seen in WS is associated with deletion of either the centromeric and/or telomeric portions of the region. Comparison of these five families with reports of other individuals with partial deletions of the WS region most strongly implicates GTF2I in the mental retardation of WS. \&copy; 2003 Wiley-Liss, Inc.}, author = {Morris, Colleen A. and Mervis, Carolyn B. and Hobart, Holly H. and Gregg, Ronald G. and Bertrand, Jacquelyn and Ensing, Gregory J. and Sommer, Annemarie and Moore, Cynthia A. and Hopkin, Robert J. and Spallone, Patricia A. and Keating, Mark T. and Osborne, Lucy and Kimberley, Kendra W. and Stock, A. Dean}, citeulike-article-id = {142710}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/ajmg.a.20496}, citeulike-linkout-1 = {http://www3.interscience.wiley.com/cgi-bin/abstract/105557828/ABSTRACT}, comment = {Colleen A. Morris, Department of Pediatrics, Division of Genetics, University of Nevada School of Medicine, Las Vegas, Nevada}, day = {17}, doi = {10.1002/ajmg.a.20496}, issn = {1552-4833}, journal = {American Journal of Medical Genetics Part A}, keywords = {7q1123, aortic, correlation, deletion, eln, genetics, genotype-phenotype, gtf2i, limk1, pediatrics, stenosis, supravalvar, syndrome, williams}, month = {September}, number = {1}, pages = {45--59}, posted-at = {2005-03-29 20:10:41}, priority = {2}, title = {GTF2I hemizygosity implicated in mental retardation in Williams syndrome: Genotype-phenotype analysis of five families with deletions in the Williams syndrome region}, url = {http://dx.doi.org/10.1002/ajmg.a.20496}, volume = {123A}, year = {2003} }

TY - JOUR ID - citeulike:142710 L3 - citeulike-article-id:142710 N2 - Most individuals with Williams syndrome (WS) have a 1.6 Mb deletion in chromosome 7q11.23 that encompasses the elastin (<I >ELN</I >) gene, while most families with autosomal dominant supravalvar aortic stenosis (SVAS) have point mutations in <I >ELN</I >. The overlap of the clinical phenotypes of the two conditions (cardiovascular disease and connective tissue abnormalities such as hernias) is due to the effect of haploinsufficiency of <I >ELN</I >. SVAS families often have affected individuals with some WS facial features, most commonly in infancy, suggesting that <I >ELN</I > plays a role in WS facial gestalt as well. To find other genes contributing to the WS phenotype, we studied five families with SVAS who have small deletions in the WS region. None of the families had mental retardation, but affected family members had the Williams Syndrome Cognitive Profile (WSCP). All families shared a deletion of <I >LIMK1</I >, which encodes a protein strongly expressed in the brain, supporting the hypothesis that <I >LIMK1</I > hemizygosity contributes to impairment in visuospatial constructive cognition. While the deletions from the families nearly spanned the WS region, none had a deletion of <I >FKBP6</I > or <I >GTF2I</I >, suggesting that the mental retardation seen in WS is associated with deletion of either the centromeric and/or telomeric portions of the region. Comparison of these five families with reports of other individuals with partial deletions of the WS region most strongly implicates GTF2I in the mental retardation of WS. &copy; 2003 Wiley-Liss, Inc. IS - 1 JF - American Journal of Medical Genetics Part A SN - 1552-4833 EP - 59 TI - GTF2I hemizygosity implicated in mental retardation in Williams syndrome: Genotype-phenotype analysis of five families with deletions in the Williams syndrome region VL - 123A SP - 45 KW - 7q1123 KW - aortic KW - correlation KW - deletion KW - eln KW - genetics KW - genotype-phenotype KW - gtf2i KW - limk1 KW - pediatrics KW - stenosis KW - supravalvar KW - syndrome KW - williams N1 - Colleen A. Morris, Department of Pediatrics, Division of Genetics, University of Nevada School of Medicine, Las Vegas, Nevada AU - Morris, Colleen AU - Mervis, Carolyn AU - Hobart, Holly AU - Gregg, Ronald AU - Bertrand, Jacquelyn AU - Ensing, Gregory AU - Sommer, Annemarie AU - Moore, Cynthia AU - Hopkin, Robert AU - Spallone, Patricia AU - Keating, Mark AU - Osborne, Lucy AU - Kimberley, Kendra AU - Stock, Dean PY - 2003/09/17/ UR - http://dx.doi.org/10.1002/ajmg.a.20496 ER -