罕见PROC基因复合杂合变异所致蛋白C缺乏症胎儿1例的临床及遗传学分析

Clinical and genetic analysis of a rare fetus with Protein C deficiency due to compound heterozygous variants of PROC gene

目的探讨1例脑积水和脑室出血胎儿的遗传学病因,为其产前诊断提供依据。方法应用全外显子组测序(WES)技术筛选与胎儿表型相符的基因变异,对候选变异进行Sanger测序验证。结果胎儿存在PROC基因c.818G>A(p.W273X)和c.833T>C(p.L278P)复合杂合变异,分别遗传自其母亲和父亲。按照美国医学遗传学与基因组学学会(ACMG)相关指南,二者均被判定为可能致病变异(PVS1_Strong+PM2_Supporting+PP4);(PM2_Supporting+PM3+PP1+PP3+PP4)。结论本研究胎儿被诊断为由PROC基因c.818G>A(p.W273X)和c.833T>C(p.L278P)复合杂合变异所致的蛋白C缺乏症。上述发现丰富了PROC基因的变异谱,为其家系的遗传咨询和产前诊断提供了依据。

Objective To explore the genetic etiology for a fetus with hydrocephalus and intraventricular hemorrhage.Methods Trio whole exome sequencing was carried out.Candidate variants were verified by Sanger sequencing of the fetus and its parents.Results The fetus was found to harbor c.818G>A(p.W273X)and c.833T>C(p.L278P)compound heterozygous variants of the PROC gene,which were respectively inherited from its mother and father.Based on the guidelines of the American College of Medical Genetics and Genomics(ACMG),both variants were predicted to be likely pathogenic(PVS1_Strong+PM2_Supporting+PP4;PM2_Supporting+PM3+PP1+PP3+PP4).Conclusion The fetus was diagnosed with Protein C deficiency due to the c.818G>A(p.W273X)and c.833T>C(p.L278P)compound heterozygous variants of the PROC gene.Above finding has enriched the spectrum of PROC gene variants and enabled genetic counseling and prenatal diagnosis for the family.