Ramírez-Velazco Azubel, Aguayo-Orozco Thania Alejandra, Figuera Luis, Rivera Horacio, Jave-Suárez Luis, Aguilar-Lemarroy Adriana, Torres-Reyes Luis A, Córdova-Fletes Carlos, Barros-Núñez Patricio, Delgadillo-Pérez Saturnino, Dávalos-Rodríguez Ingrid Patricia, García-Ortiz José Elías, Domínguez María G
División de Genética, CIBO Instituto Mexicano del Seguro Social Guadalajara México.
J Genet. 2019 Jun;98(2).
Williams-Beuren syndrome (WBS) has a prevalence of 1/7500-20000 live births and results principally from a deletion in 7q11.23 with a length of 1.5 Mb or 1.8 Mb. This study aimed to determine the frequency of 7q11.23 deletion, size of the segment lost, and involved genes in 47 patients with a clinical diagnosis of WBS and analysed by fluorescence in situ hybridization (FISH); among them, 31 had the expected deletion. Micro-array comparative genomic hybridization (aCGH) confirmed the loss in all 18 positive-patients tested: 14 patients had a 1.5 Mb deletion with the same breakpoints at 7q11.23 (hg19: 72726578-74139390) and comprising 24 coding genes from to . Four patients showed an atypical deletion: two had a 1.6 Mb loss encompassing 27 coding genes, from to ; another had a 1.7 Mb deletion involving 27 coding genes, from to ; the remaining patient presented a deletion of 1.2 Mb that included 21 coding genes from to . aCGH confirmed the lack of deletion in 5/16 negative-patients by FISH. All 47 patients had the characteristic facial phenotype of WBS and 45 of 47 had the typical behavioural and developmental abnormalities. Our observations further confirm that patients with a classical deletion present a typical WBS phenotype, whereas those with a high (criteria of the American Association of Pediatrics, APP) clinical score but lacking the expected deletion may harbour an ELN point mutation. Overall, the concomitant CNVs appeared to be incidental findings.
威廉姆斯-贝伦综合征（WBS）在活产婴儿中的患病率为1/7500至1/20000，主要由7q11.23区域长度为1.5 Mb或1.8 Mb的缺失所致。本研究旨在确定47例临床诊断为WBS且通过荧光原位杂交（FISH）分析的患者中7q11.23缺失的频率、缺失片段的大小以及受累基因；其中31例有预期的缺失。微阵列比较基因组杂交（aCGH）证实了所有18例检测为阳性的患者存在缺失：14例患者有1.5 Mb的缺失，其断点位于7q11.23（hg19: 72726578 - 74139390），包含从 到 的24个编码基因。4例患者表现出非典型缺失：2例有1.6 Mb的缺失，涵盖从 到 的27个编码基因；另1例有1.7 Mb的缺失，涉及从 到 的27个编码基因；其余1例患者有1.2 Mb的缺失，包括从 到 的21个编码基因。aCGH证实了16例FISH检测为阴性的患者中有5例不存在缺失。所有47例患者均有WBS的特征性面部表型，47例中有45例有典型的行为和发育异常。我们的观察结果进一步证实，具有经典缺失的患者表现出典型的WBS表型，而那些临床评分高（美国儿科学会，APP标准）但缺乏预期缺失的患者可能存在ELN点突变。总体而言，伴随的拷贝数变异似乎是偶然发现。
