POMT1基因新型复合杂合突变导致的1个Walker-Warburg综合征家系的产前诊断

Prenatal diagnosis of a Walker-Warburg syndrome pedigree due to novel compound heterozygous mutations in the POMT1 gene

目的对1例Walker-Warburg综合征胎儿进行产前诊断,明确其致病原因。方法选取在临沂市妇幼保健院就诊的1例连续5次妊娠脑积水患儿的孕妇作为研究对象,收集其临床信息。采集羊水标本以及孕妇夫妇的外周血样,进行染色体微阵列分析(CMA)和全外显子组测序,并用Sanger测序对候选变异进行验证。结果孕21周超声提示胎儿出现严重的脑积水。胎儿CMA检测未见异常。基因测序提示胎儿蛋白O-甘露糖基转移酶1(protein O-mannosyltransferase 1,POMT1)基因存在母源NM_001077365.2:c.1665delC(p.Asn556fs)和父源NM_001077365.2:c.797T>A(p.Val266Asp)变异。根据美国医学遗传学与基因组学学会变异相关指南,c.1665delC被评级为致病性变异,c.797T>A被评级为可能致病性变异。结论POMT1基因c.1665delC和c.797T>A变异可能是家系反复出现脑积水患儿的遗传学病因。

Objective This study aimed to conduct prenatal diagnosis on a fetus with Walker-Warburg syndrome to elucidate its pathogenic cause.Methods A pregnant woman with a history of five consecutive episodes of hydrocephalus at the Women and Children’s Hospital of Linyi City was chosen as the subject.Clinical data was collected,and amniotic fluid and peripheral blood samples were obtained from the pregnant couple for chromosome microarray analysis(CMA)and whole exome sequencing.Candidate variants were validated using Sanger sequencing.Results Ultrasound at 21 weeks of pregnancy revealed severe hydrocephalus in the fetus.Fetal CMA testing did not show any abnormalities.Genetic sequencing identified maternal NM_001077365.2:c.1665delC(p.Asn556fs)and paternal NM_001077365.2:c.797T>A(p.Val266Asp)variants in the fetal protein O-mannosyltransferase 1(POMT1)gene.According to the American Society of Medical Genetics and Genomics guidelines,c.1665delC was classified as a pathogenic variant,while c.797T>A was considered a possible pathogenic variant.Conclusion The c.1665delC and c.797T>A mutations in the POMT1 gene may be responsible for the recurrent hydrocephalus observed in the family’s children.