Yan Lulu, Huo Yifan, Liu Yingwen, Zhang Yuxin, Han Chunxiao, Cao Juan, Li Haibo
Ningbo Women and Children's Hospital, the Central Laboratory of Birth Defects Prevention and Control, Ningbo, Zhejiang 315012, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2023 Nov 10;40(11):1330-1333. doi: 10.3760/cma.j.cn511374-20220704-00449.
To explore the genetic etiology for a fetus with hydrocephalus and intraventricular hemorrhage.
Trio whole exome sequencing was carried out. Candidate variants were verified by Sanger sequencing of the fetus and its parents.
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).
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.
探讨一名患有脑积水和脑室内出血胎儿的遗传病因。
进行三联体全外显子测序。通过对胎儿及其父母进行桑格测序验证候选变异。
发现该胎儿携带PROC基因的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。根据美国医学遗传学与基因组学学会（ACMG）的指南，这两个变异均被预测可能致病（PVS1_强+PM2_支持+PP4；PM2_支持+PM3+PP1+PP3+PP4）。
该胎儿因PROC基因的c.818G>A（p.W273X）和c.833T>C（p.L278P）复合杂合变异被诊断为蛋白C缺乏症。上述发现丰富了PROC基因变异谱，并为该家庭提供了遗传咨询和产前诊断。
