FSHR剪切变异c.299+2T>G致卵巢抵抗综合征的家系分析  

Identification of a novel splice variant c.299+2T>G of FSHR in a pedigree affected with resistant ovary syndrome

作　　者：闫慧[1,2] 黄蕾 马小红 哈灵侠[1,2] 赵君利[1,2] 张倩 闫有圣[3] 刘春莲[1,2] YAN Hui;HUANG Lei;MA Xiao-hong;HA Ling-xia;ZHAO Jun-li;ZHANG Qian;YAN You-sheng;LIU Chun-lian(Center for Reproductive Medicine,General Hospital of Ningxia Medical University,Yinchuan 750004;Key Laboratory of Fertility Preservation and Maintenance,Ministry of Education,Yinchuan 750004;Prenatal Diagnostic Center,Beijing Obstetrics and Gynecology Hospital,Capital Medical University,Beijing 100026)

机构地区：[1]宁夏医科大学总医院生殖医学中心,银川750004 [2]生育力保持教育部重点实验室,银川750004 [3]首都医科大学附属北京妇产医院产前诊断中心,北京100026

出　　处：《生殖医学杂志》2023年第2期245-251,共7页Journal of Reproductive Medicine

基　　金：宁夏高等学校一流学科建设(宁夏医科大学国内一流建设学科临床医学)资助项目。

摘　　要：目的探讨卵巢抵抗综合征(ROS)不孕患者的遗传学病因,为临床遗传咨询及助孕方案提供诊疗依据。方法收集先证者家系临床资料及遗传学检测指标,绘制家系图谱,进行染色体G显带核型分析,应用高通量基因测序技术(NGS)进行全外显子组测序;对先证者父母与兄长的变异位点进行Sanger测序验证,并进行生物信息学分析及诊断。结果该女性先证者临床诊断为原发性闭经、ROS;先证者母亲的祖母与父亲的祖父为亲兄妹。全外显子组测序及Sanger测序检测到先证者存在卵泡刺激素受体(FSHR)基因经典剪切变异NM_000145.4 c.299+2T>G(纯合型),且该变异为未报道的致病性变异;其兄长该位点突变与先证者一致,其父母均存在FSHR剪切变异c.299+2T>G(杂合型)。结论FSHR新发现的剪切变异c.299+2T>G的检出,丰富了FSHR基因突变谱,为ROS的临床治疗和家系成员的遗传咨询提供了参考。Objective:To investigate the genetic etiology of infertile patients with resistant ovary syndrome(ROS),and to provide the basis for clinical genetic counseling and assisted pregnancy protocol.Methods:The clinical data and genetic indexes of the proband’s family were collected,and the family map was drawn.Chromosome karyotype analysis of G-banding was carried out,and the whole exome was sequenced by the next-generation sequencing technology(NGS).Sanger verification was performed on the mutation sites of the proband’s parents and elder brother,and bioinformatics analysis and diagnosis were performed.Results:The female proband was clinically diagnosed as primary amenorrhea and ROS.The proband’s mother’s grandmother and father’s grandfather are siblings.Whole-exome sequencing and Sanger sequencing detected that the proband had classical splice variant NM_000145.4 c.299+2T>G of FSH receptor(FSHR)gene(homozygous),and the variant is an unreported pathogenic variant.The mutation of this site in her elder brother is consistent with the proband,and her parents all have splice variant of c.299+2T>G of FSHR(heterozygous type).Conclusions:A novel splice variant c.299+2T>G of FSHR is detected,which enriches the mutation spectrum of FSHR gene and provides a basis for clinical treatment of ROS and genetic counseling of family members.

关 键 词：卵巢抵抗综合征 基因测序 FSHR基因 剪切变异 

分 类 号：R715.5[医药卫生—妇产科学]