Lowery M C, Morris C A, Ewart A, Brothman L J, Zhu X L, Leonard C O, Carey J C, Keating M, Brothman A R
Department of Pediatrics, University of Utah Health Sciences Center, Salt Lake City, UT 84132, USA.
Am J Hum Genet. 1995 Jul;57(1):49-53.
Williams syndrome (WS) is generally characterized by mental deficiency, gregarious personality, dysmorphic facies, supravalvular aortic stenosis, and idiopathic infantile hypercalcemia. Patients with WS show allelic loss of elastin (ELN), exhibiting a submicroscopic deletion, at 7q11.23, detectable by FISH. Hemizygosity is likely the cause of vascular abnormalities in WS patients. A series of 235 patients was studied, and molecular cytogenetic deletions were seen in 96% of patients with classic WS. Patients included 195 solicited through the Williams Syndrome Association (WSA), plus 40 clinical cytogenetics cases referred by primary-care physicians. Photographs and medical records of most WSA subjects were reviewed, and patients were identified as "classic" (n = 114) or "uncertain" (n = 39). An additional 42 WSA patients were evaluated without clinical information. FISH was performed with biotinylated ELN cosmids on metaphase cells from immortalized lymphoblastoid 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 allele; four of these did not show a deletion. Of the uncertain WS patients, only 3 of 39 showed a deletion. Of the 42 who were not classified phenotypically, because of lack of clinical information, 25 patients (60%) showed a deletion. Thirty-eight percent (15/40) of clinical cytogenetics 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.
威廉姆斯综合征（WS）通常具有智力缺陷、外向型人格、面部畸形、主动脉瓣上狭窄以及特发性婴儿高钙血症等特征。WS患者表现出弹力蛋白（ELN）的等位基因缺失，在7q11.23处存在亚显微缺失，可通过荧光原位杂交（FISH）检测到。半合子状态可能是WS患者血管异常的原因。对235例患者进行了研究，96%的典型WS患者存在分子细胞遗传学缺失。患者包括通过威廉姆斯综合征协会（WSA）招募的195例，以及初级保健医生转诊的40例临床细胞遗传学病例。对大多数WSA受试者的照片和病历进行了审查，患者被分为“典型”（n = 114）或“不确定”（n = 39）。另外42例WSA患者在没有临床信息的情况下进行了评估。使用生物素化的ELN黏粒对WSA患者永生化淋巴母细胞系的中期细胞进行FISH检测，并对临床转诊患者进行高分辨率显带分析。杂交中包含7号染色体的α卫星探针作为内部对照。96%的典型WS患者在一个ELN等位基因中显示缺失；其中4例未显示缺失。在不确定的WS患者中，39例中只有3例显示缺失。在因缺乏临床信息而未进行表型分类的42例患者中，25例（60%）显示缺失。38%（15/40）的临床细胞遗传学病例显示ELN缺失，而通过显带分析未发现细胞遗传学缺失。这些结果支持FISH在检测弹力蛋白缺失作为WS初步诊断检测方法中的有用性。
