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.
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Williams syndrome is caused by a deletion of 25-30 genes in the q11.23 region of chromosome 7 that spans approximately 1.5 megabases.
“The cause of this disorder has been determined to be a deletion of 25–30 genes in the q11.23 region of either maternal or paternal chromosome 7 that spans approximately 1.5 megabases (Ewart et al., 1993; Korenberg et al., 2000; Lowery et al., 1995; Schubert, 2009).”
From Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders (2014) · cites this paper as Ewart et al., 1993
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- Authors
- Ewart, A. K., Morris, C. A., Atkinson, D., Jin, W., Sternes, K., Spallone, P., Stock, A. D., Leppert, M., & Keating, M. T.
- Affiliations
- University of Utah (US)
- University of Nevada, Las Vegas (US)
- University of Nevada, Reno (US)
- Howard Hughes Medical Institute (US)
- Venue
- Nature Genetics
- Published
- 1993-09
- Volume
- 5
- Issue
- 1
- Pages
- 11-16
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1992752077
- Cited by
- 1,138
- References
- 26
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 20 · 2023: 15 · 2022: 14 · 2021: 50 · 2020: 19 · 2019: 26 · 2018: 25 · 2017: 30 · 2016: 25 · 2015: 39 · 2014: 33 · 2013: 38 · 2012: 42
- FWCI
- 8.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL4807)
- National Center for Research Resources (MO1-RR-00064, M01RR000064)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Williams syndrome, elastin gene, hemizygosity, supravalvular aortic stenosis, developmental disorders, connective tissue diseases, de novo deletion, gene dosage, pathogenesis
- MeSH terms
- Adult, Alleles, Aortic Valve Stenosis, Arteries, Child, Developmental Disabilities, Child, Preschool, Chromosomes, Human, Pair 7, Connective Tissue Diseases, Elastin, Genes, Genotype, Humans, Intellectual Disability, Pedigree, Syndrome, Blotting, Southern, Sequence Deletion, In Situ Hybridization, Fluorescence
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