title: Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome.
abstract: Williams syndrome (WS) is a developmental disorder affecting connective tissue and the central nervous system. A common feature of WS, supravalvular aortic stenosis, is also a distinct autosomal dominant disorder caused by mutations in the elastin gene. In this study, we identified hemizygosity at the elastin locus using genetic analyses in four familial and five sporadic cases of WS. Fluorescent in situ hybridization and quantitative Southern analyses confirmed these findings, demonstrating inherited and de novo deletions of the elastin gene. These data indicate that deletions involving one elastin allele cause WS and implicate elastin hemizygosity in the pathogenesis of the disease.
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City 84112.
authors.forename: A K
authors.initials: AK
authors.lastname: Ewart
authors.forename: C A
authors.initials: CA
authors.lastname: Morris
authors.forename: D
authors.initials: D
authors.lastname: Atkinson
authors.forename: W
authors.initials: W
authors.lastname: Jin
authors.forename: K
authors.initials: K
authors.lastname: Sternes
authors.forename: P
authors.initials: P
authors.lastname: Spallone
authors.forename: A D
authors.initials: AD
authors.lastname: Stock
authors.forename: M
authors.initials: M
authors.lastname: Leppert
authors.forename: M T
authors.initials: MT
authors.lastname: Keating
mesh_terms: D000328:Adult; D000483:Alleles; D001024:Aortic Valve Stenosis / Q000235:genetics; D001158:Arteries / Q000002:abnormalities; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D002897:Chromosomes, Human, Pair 7; D003240:Connective Tissue Diseases / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D004549:Elastin / Q000235:genetics*; D005796:Genes; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics; D010375:Pedigree; D017384:Sequence Deletion; D013577:Syndrome
chemical_list: D004549:Elastin