Microdeletion of Chromosome 7 in Williams Syndrome and Supravalvular Aortic Stenosis

ABSTRACT

PURPOSE: Williams syndrome is characterized by supravalvular aortic stenosis, mental retardation and peculiar facial appearance. Its genetic etiology is considered to be a hemizygotic deletion in Chromosome 7q11.23, which includes the elastin gene. We examined the hemizygotic deletion of Chromosome 7q11.23 in 12 Korean Williams syndrome patients and 8 patients with isolated supravalvular aortic stenosis and performed deletion mapping in the Williams syndrome patients. METHODS: Hemizygotic deletion was determined with fluorescence in situ hybridization(FISH) using the bacterial artificial chromosome clone 244H3, which has the genomic DNA sequence of elastin gene, as a probe. For the deletion mapping, polymorphism analysis of 10 Williams syndrome patients and their parents was done with 9 dinucleotide repeat sequence polymorphic markers(D7S499, D7S672, D7S653, ELN, D7S2472, D7S1870, D7S2518, D7S675 and D7S669). RESULTS: In the Williams syndrome patients, FISH showed deletion in all. In patients with isolated supravalvular aortic stenosis, FISH showed deletion in one, partial deletion in another and no deletion in the other six patients. Polymorphism analysis showed that alleles at three loci(ELN, D7S2472 and D7S1870) were commonly deleted in the Williams syndrome patients. Paternal alleles were deleted in six patients and maternal alleles were deleted in four. CONCLUSION: Hemizygotic deletion could be detected in Williams syndrome patients with FISH and the commonly deleted loci were ELN, D7S2472 and D7S1870. Most patients with isolated supravalvular aortic stenosis showed no deletion with FISH and the genetic defect should be much smaller than what FISH could detect.