Walker-Warburg综合征胎儿1例的产前诊断

Prenatal diagnosis for a fetus with Walker-Warburg syndrome

目的探讨1例Walker-Warburg综合征(WWS)胎儿的遗传学特征。方法选取2021年6月9日至甘肃省妇幼保健院确诊的1例WWS胎儿为研究对象,采集胎儿羊水及其父母和姐姐的外周血样,提取基因组DNA,进行trio-WES检测,用Sanger测序对候选变异进行家系验证。结果Trio-WES检测显示胎儿POMT2基因存在第4外显子c.471delC(p.F158Lfs*42)移码变异和第20外显子的c.1975C>T(p.R659W)错义变异,分别遗传自父亲和母亲。根据美国医学遗传学与基因组学学会(ACMG)相关指南分别判定为致病性变异(PVS1+PM2Supporting+PP4)和可能致病性变异(PM2Supporting+PM3+PP3Moderate+PP4)。结论产前诊断中应用trio-WES检测可快速可靠的确诊WWS患儿,为临床决策发挥重要作用。同时,发现POMT1基因1种新变异,在国内外未见报道。扩充了POMT2基因致病变异谱,为疾病的临床诊断和遗传咨询提供理论依据。

Objective To explore the genetic etiology for a fetus with Walker-Warburg syndrome(WWS).Methods 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.Results 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).Conclusion 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.