Nature Genetics
5, 11 - 16 (1993)
doi:10.1038/ng0993-11
Hemizygosity at the elastin locus in a developmental disorder, Williams syndromeAmanda K. Ewart1, Colleen A. Morris5, 7, Donald Atkinson1, Weishan Jin1, Keith Sternes6, Patricia Spallone8, A. Dean Stock7, 8, Mark Leppert1, 3
& Mark T. Keating1, 2, 4
1Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112, USA
2Cardiology Division, University of Utah, Salt Lake City, Utah 84112, USA
3Howard Hughes Medical Institute, University of Utah, Salt Lake City, Utah 84112, USA
4Eccles Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah 84112, USA
5Department of Pediatrics, University of Nevada School of Medicine, Las Vegas, Nevada 89102, USA
6Department of Microbiology, University of Nevada School of Medicine, Reno, Nevada 89502, USA
7Department of Pathology and Laboratory Medicine, University of Nevada School of Medicine, Reno, Nevada 89502, USA
8Genetics Network, University of Nevada School of Medicine, Reno, Nevada 89502, USA 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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