WEE2基因c.495del纯合移码变异引起受精障碍导致女性不孕一个家系的分析  

Analysis of a Chinese pedigree with female infertility due to WEE2 gene c.495del homozygous frameshifting variant induced fertilization disorder

作　　者：杨金伟 王志强[1] 郭雅琼 晏博 丁仲军 倪亚莉[1] Yang Jinwei;Wang Zhiqiang;Guo Yaqiong;Yan Bo;Ding Zhongjun;Ni Yali(Center for Reproductive Medicine,Gansu Provincial Maternal and Child Health Care Hospital(Gansu Provincial Central Hospital),Lanzhou,Gansu 730050,China;Department of Clinical Laboratory,the Second People′s Hospital of Gansu Province,Lanzhou,Gansu 730000,China)

机构地区：[1]甘肃省妇幼保健院(甘肃省中心医院)生殖医学中心,兰州730050 [2]甘肃省第二人民医院检验科,兰州730000

出　　处：《中华医学遗传学杂志》2024年第12期1478-1482,共5页Chinese Journal of Medical Genetics

基　　金：甘肃省自然科学基金(22JR5RA735、23JRRA1389);兰州市科技计划(2022-ZD-66)。

摘　　要：目的探索1例反复受精失败患者的遗传学病因,明确变异的来源和遗传方式。方法选取2024年1月因"原发不孕6年,左侧输卵管不全梗阻"就诊于甘肃省妇幼保健院生殖医学中心的1对夫妇作为研究对象,收集相关临床资料。采用全外显子组测序技术对双方进行检测,对候选变异位点用Sanger测序进行家系验证,通过生物信息学分析预测其致病性。本研究通过了甘肃省妇幼保健院医学伦理委员会的审查(批准号:2023GSFYLS78)。结果女方检测发现WEE2基因c.495del纯合移码变异,男性未检测到与表型有关的疑似致病变异。女方哥哥携带同样的纯合变异,其父母、大姨、大姑、小叔、外婆和奶奶均为杂合子。按照美国医学遗传学与基因组学学会相关指南,上述变异被判定为致病性。结论WEE2基因c.495del纯合移码变异可能是该例夫妇卵母细胞受精障碍的遗传学病因。ObjectiveTo explore the genetic basis for a patient with repeated fertilization failure during assisted reproductive therapy,and to identify the source and mode of mutation.MethodsA couple treated at the Center for Reproductive Medicine,Gansu Provincial Maternal and Child Health Care Hospital in January 2024 for infertility with incomplete left tube obstruction was selected as the study subject.Relevant clinical data was collected.The couple was subjected to whole exome sequencing(WES),and the candidate variant was verified by Sanger sequencing of their family members and bioinformatic analysis.The study has been approved by the the Center for Reproductive Medicine,Gansu Provincial Maternal and Child Health Care Hospital(Ethic No.2023GSFYLS78).ResultsWES has identified a homozygous c.495del frameshifting mutation of the WEE2 gene in the female partner,whilst no relevant variant was suspected in the male partner.The elder brother of the female partner was homozygous for the above variant,while her parents,aunts,uncle,grandmother,and grandmother were heterozygous for it.Based on the guidelines from the American College of Medical Genetics and Genomics,above variant was rated to be pathogenic.ConclusionThe homozygous c.495del frameshifting mutation of the WEE2 gene probably underlay the oocyte fertilization disorder in this couple.

关 键 词：受精失败 女性不孕 WEE2基因 全外显子组测序 

分 类 号：R711.6[医药卫生—妇产科学]