HEMIZYGOSITY AT THE ELASTIN LOCUS IN A DEVELOPMENTAL DISORDER, WILLIAMS-SYNDROME

Williams syndrome (WS) is a developmental disorder affecting connectiv e tissue and the central nervous system. A common feature of WS, supra valvular aortic stenosis, is also a distinct autosomal dominant disord er caused by mutations in the elastin gene. In this study, we identifi ed hemizygosity at the elastin locus using genetic analyses in four fa milial and five sporadic cases of WS. Fluorescent in situ hybridizatio n and quantitative Southern analyses confirmed these findings, demonst rating inherited and de novo deletions of the elastin gene. These data indicate that deletions involving one elastin allele cause WS and imp licate elastin hemizygosity in the pathogenesis of the disease.