Ma Panpan, Chen Xue, Hui Ling, Zhang Qinghua, Zhang Chuan, Hao Shengju, Yang Lan, Wang Xing, Xu Furong, Zhou Bingbo
Medical Genetics Center, Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Gansu Provincial Maternity and Child Health Care Hospital, Lanzhou, Gansu 730050, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2023 May 10;40(5):572-576. doi: 10.3760/cma.j.cn511374-20220425-00279.
To explore the genetic etiology for a fetus with Walker-Warburg syndrome(WWS).
A fetus with WWS diagnosed at Gansu Provincial Maternity and Child Health Care Hospital in June 9, 2021 was selected as the study subject. Genomic DNA was extracted from amniotic fluid sample of the fetus and peripheral blood samples from its parents. Trio-Whole exome sequencing (trio-WES) was carried out. Candidate variants were verified by Sanger sequencing.
The fetus was found to harbor compound heterozygous variants of the POMT2 gene, namely c.471delC (p.F158Lfs*42) and c.1975C>T (p.R659W), which were respectively inherited from its father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively rated as pathogenic (PVS1+PM2_Supporting+PP4) and likely pathogenic (PM2_Supporting+PM3+PP3_Moderate+PP4).
Trio-WES may be used for the prenatal diagnosis of WWS. The compound heterozygous variants of the POMT2 gene probably underlay the disorder in this fetus. Above finding has expanded the mutational spectrum of the POMT2 gene and enabled definite diagnosis and genetic counseling for the family.
探讨一名患有沃克 - 沃伯格综合征（WWS）胎儿的遗传病因。
选取2021年6月9日在甘肃省妇幼保健院诊断为WWS的一名胎儿作为研究对象。从该胎儿的羊水样本及其父母的外周血样本中提取基因组DNA。进行三联全外显子测序（trio-WES）。通过桑格测序验证候选变异。
发现该胎儿携带POMT2基因的复合杂合变异，即c.471delC（p.F158Lfs*42）和c.1975C>T（p.R659W），分别遗传自其父亲和母亲。根据美国医学遗传学与基因组学学会（ACMG）的指南，它们分别被评为致病（PVS1+PM2_Supporting+PP4）和可能致病（PM2_Supporting+PM3+PP3_Moderate+PP4）。
三联全外显子测序可用于WWS的产前诊断。POMT2基因的复合杂合变异可能是该胎儿疾病的病因。上述发现扩展了POMT2基因的突变谱，并为该家庭提供了明确诊断和遗传咨询。
