摘要
目的:分析1例无头精子症造成的原发性男性不育症患者的临床特点和遗传学病因。方法:选取2022年10月1日就诊于河南省人民医院生殖中心的1例男性不育症患者作为研究对象。收集患者夫妇的临床信息、实验室以及精子的电镜检查结果。对患者进行全外显子组测序分析,并对候选致病位点进行Sanger测序家系验证和致病性分析。结果:全外显子组测序显示患者携带PMFBP1基因c.853del(p.Ala285Leufs*24)和c.1276A>T(p.Lys426X)复合杂合变异,既往均未见报道。Sanger测序的结果提示c.853del(p.Ala285Leufs*24)变异遗传自患者已去世的母亲,c.1276A>T(p.Lys426X)变异遗传自父亲。根据美国医学遗传学与基因组学学会相关指南,上述变异均被判定为致病性(PVS1+PM2_Supporting+PP4)。结论:PMFBP1基因变异可能是患者的遗传学病因。新变异的检出丰富了人类无头精子症的致病突变谱。
Objective To analyze the clinical characteristics and genetic basis of a male patient with primary infertility caused by Acephalic spermatozoa syndrome.Methods A patient who had presented at the Henan Provincial People′s Hospital on October 1,2022 was selected as the study subject.Clinical data and results of laboratory exams and sperm electron microscopy were collected.The patient was subjected to whole exome sequencing(WES),and candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results WES revealed that the patient has harbored compound heterozygous variants of the PMFBP1 gene,namely c.853del(p.Ala285Leufs*24)and c.1276A>T(p.Lys426X),which were both unreported previously.Sanger sequencing suggested that the c.853del(p.Ala285Leufs*24)variant has derived from his deceased mother,whilst the c.1276A>T(p.Lys426X)variant has derived from his father.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),both variants were classified as pathogenic(PVS1+PM2_Supporting+PP4).Conclusion The compound heterozygous variants of the PMFBP1 gene probably underlay the Acephalic spermatozoa syndrome in this patient.The discovery of the novel variants has also enriched the mutational spectrum of Acephalic spermatozoa syndrome.
作者
冯科
夏彦清
曲晓伟
万锋
杨科
徐嘉宁
张翠莲
郭海彬
Feng Ke;Xia Yanqing;Qu Xiaowei;Wan Feng;Yang Ke;Xu Jianing;Zhang Cuilian;Guo Haibin(Center for Reproductive Medicine,Henan Provincial People′s Hospital,People′s Hospital of Zhengzhou University,Henan Provincial People′s Hospital of Henan University,Henan Joint International Research Laboratory for Reproductive Bioengineering,Zhengzhou,Henan 450003,China;Medical Genetic Institute of Henan Province,Zhengzhou,Henan 450003,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2024年第6期749-752,共4页
Chinese Journal of Medical Genetics
基金
河南省医学科技攻关计划(联合共建)项目(LHGJ20230067、LHGJ20230046)。
