DELETIONS OF THE ELASTIN GENE AT 7Q11.23 OCCUR IN SIMILAR-TO-90-PERCENT OF PATIENTS WITH WILLIAMS-SYNDROME

To investigate the frequency of deletions of the elastin gene in patie nts with Williams syndrome (WS), we screened 44 patients by both FISH and PCR amplification of a dinucleotide repeat polymorphism FISH was p erformed using cosmids containing either the 5' or the 3' end of the e lastin gene. PCR analysis was performed on the patients and their pare nts with a (CA), repeat polymorphism found in intron 17 of the elastin locus. Of the 44 patients screened, 91% were shown to be deleted by F ISH. Using the DNA polymorphism, both maternally (39%) and paternally (61%) derived deletions were found. Four patients were not deleted for eIastin but have clinical features of WS. Since deletions of elastin cannot account for several features found in WS, these patients will b e valuable in further delineation of the critical region responsible f or the WS phenotype. Although PCR can be useful for determining the pa rental origin of the deletion, our results demonstrate that FISH analy sis of the elastin locus provides a more rapid and informative test to confirm a clinical diagnosis of WS. The presence of two copies of the elastin locus in a patient does not, however, rule out WS as a diagno sis.