NLRP7基因变异致复发性葡萄胎一个家系的遗传学分析

Genetic analysis of a family with recurrent hydatidiform mole caused by NLRP7 gene mutation

复发性葡萄胎指同一患者发生2次或以上的葡萄胎,常与家族性或散发性双亲来源完全性葡萄胎有关,已有研究表明该疾病与NLRP7和KHDC3L基因突变有关。本院生殖医学中心接收1例因2次葡萄胎史要求助孕患者,收集该家系临床资料,抽取患者及其家属成员的外周血样进行全外显子测序和Sanger验证。全外显子组测序结果显示先证者NLRP7基因存在c.2282G>A(p.Cys761Tyr)纯合突变,Sanger测序结果与其一致;Sanger验证其父母和姐姐是该变异的杂合携带者。先证者通过卵子捐赠和卵胞质内单精子注射技术最终获得临床妊娠。因此,NLRP7基因c.2282G>A(p.Cys761Tyr)纯合突变是导致该患者复发性葡萄胎的遗传学病因,该变异的发现拓宽了NLRP7基因致病变异谱,可进一步为该类患者提供生育指导。

Recurrent hydatidiform moles refer to patients with at least two molar pregnancies.Mutations in NLRP7 and KHDC3L genes have been implicated in this disease.A pedigree with a history of recurrent hydatidiform mole who visited Tianjin Medical University General Hospital Reproductive Medicine Center,was selected as the study subject.Clinical data of the family member were collected,peripheral blood samples were taken from each member.Whole exon sequencing was carried out for the proband.Candidate genes were validated by Sanger sequencing of her family members.The whole exome sequencing showed that the proband had a homozygous mutation of c.2282G>A(p.Cys761Tyr)in the NLRP7 gene,the Sanger sequencing results were consistent with the results.Sanger sequencing results verified that the parents and her sisters carried heterozygous mutations.The proband obtained a clinical pregnancy through egg donation and intracytoplasmic sperm injection.Therefore,homozygous mutation of NLRP7 gene c.2282G>A(p.Cys761Tyr)is the genetic cause of recurrent hydatidiform mole.The discovery of this mutation broadens the spectrum of NLRP7 gene pathogenic variants and provide fertility guidance for such patients.