STRONG CORRELATION OF ELASTIN DELETIONS, DETECTED BY FISH, WITH WILLIAMS-SYNDROME - EVALUATION OF 235 PATIENTS

Williams syndrome (WS) is generally characterized by mental deficiency , gregarious personality, dysmorphic facies, supravalvular aortic sten osis, and idiopathic infantile hypercalcemia. Patients with WS show al lelic loss of elastin (ELN), exhibiting a submicroscopic deletion, at 7q11.23, detectable by FISH. Hemizygosity is likely the cause of vascu lar abnormalities in WS patients. A series of 235 patients was studied , and molecular cytogenetic deletions were seen in 96% of patients wit h classic WS. Patients included 195 solicited through the Williams Syn drome Association (WSA), plus 40 clinical cytogenetics cases referred by primary-care physicians. Photographs and medical records of most WS A subjects were reviewed, and patients were identified as ''classic'' (n = 114) of ''uncertain'' (n = 39). An additional 42 WSA patients wer e evaluated without clinical information. FISH was performed with biot inylated ELN cosmids on metaphase cells from immortalized lymphoblasto id lines from WSA patients and after high-resolution banding analysis on clinical referral patients. An alpha-satellite probe for chromosome 7 was included in hybridizations, as an internal control. Ninety-six percent of the patients with classic WS showed a deletion in one ELN a llele; four of these did not show a deletion. Of the uncertain WS pati ents, only 3 of 39 showed a deletion. Of the 42 who were not classifie d phenotypically, because of lack of clinical information, 25 patients (60%) showed a deletion. Thirty-eight percent (15/40) of clinical cyt ogenetics cases showed an ELN deletion and no cytogenetic deletion by banded analysis. These results support the usefulness of FISH for the detection of elastin deletions as an initial diagnostic assay for WS.