男性性腺功能减退症的致病基因分析  

Genetic analysis of male hypogonadism

作　　者：李翠[1] 王晓岩 刘小刚 李萍萍 赵明刚[1] 薛梅 王翔[1] LI Cui;WANG Xiao-yan;LIU Xiao-gang;LI Ping-ping;ZHAO Ming-gang;XUE Mei;WANG Xiang(Center for Translational Medicine,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China;Department of Clinical Laboratory,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China)

机构地区：[1]西安交通大学第一附属医院转化医学中心,陕西西安710061 [2]西安交通大学第一附属医院检验科,陕西西安710061

出　　处：《生物技术》2022年第6期721-725,748,共6页Biotechnology

基　　金：陕西省自然科学基础研究计划项目(2020JQ-533);西安交通大学第一附属医院院基金资助项目(2018MS-15)。

摘　　要：[目的]通过全外显子组测序(WES)技术筛选男性性腺功能减退症的致病基因,并对基因突变位点进行生物信息学分析。[方法]收集5例男性性腺功能减退症患者临床及遗传学检测资料。采用WES技术筛选相关致病基因,并通过PCR扩增、Sanger测序以及生物信息学分析等验证突变位点。[结果]先证者1为PROKR2基因c.533G>C(p.W178S)纯合突变,家系验证结果发现其父母均为PROKR2基因c.533G>C(p.W178S)杂合突变携带者,符合常染色体隐性遗传。先证者2为ZFPM2基因c.1498C>G(p.Q500E)杂合突变,生物信息学分析发现,该突变位点编码的氨基酸在不同物种中高度保守,并在人类外显子数据库、参考人群千人基因组1000G、SNP数据库及人群基因组突变频率数据库中未发现该突变位点,该突变经SIFT、Polyphen2和Mutation Taster软件预测结果均为有害。[结论]PROKR2基因c.533G>C(p.W178S)和ZFPM2基因c.1498C>G(p.Q500E)突变可能是男性性腺功能减退症的致病原因。[Objective]To screen the pathogenic genes of patients with male hypogonadism through whole exome sequencing,and to analyze the mutations by bioinformatics.[Method]The clinical data and genetic test were collected in 5 patients with male hypogonadism.The mutant genes were captured by whole exome sequencing,and analyzed with PCR,Sanger sequencing and bioinformatics analysis.[Result]A homozygous mutation c.533 G>C(p.W178 S)of PROKR2 gene was detected in proband 1.Pedigree analysis revealed that his parents were heterozygous mutation carriers of c.533 G>C(p.W178 S)in PROKR2 gene.A heterozygous mutation c.1498 C>G(p.Q500 E)of ZFPM2 gene in proband 2 was found by whole exome sequencing.Bioinformatics analysis showed that the amino acid encoded by the mutation site is highly conserved in different organisms.And the mutation site has not been found in the ExAC database,the 1000 Genomes Project database,dbSNP and the Genome Aggregation Database.This missense p.Q500 E mutation was predicted to be damaging or possibly damaging by SIFT,Polyphen2 and Mutation Taster.[Conclusion]The mutation c.533 G>C(p.W178 S)in PROKR2 gene and c.1498 C>G(p.Q500 E)of ZFPM2 gene could be associated with male hypogonadism,respectively.

关 键 词：性腺功能减退 全外显子组测序 基因突变 生物信息学分析 

分 类 号：R446.9[医药卫生—诊断学]