KISS1R基因突变所致的一个特发性低促性腺激素性性腺功能减退症家系分析  

KISS1R gene mutation analysis in a family with idiopathic hypogonadotropic hypogonadism

作　　者：周庆菊[1] 杨利[1] 赵红燕[1] 何丽[1] 陈晓[1] 李岱[1] 敬媛媛[1] 吴凡[1] 李蓉[1] 

机构地区：[1]重庆医科大学附属第一医院内分泌科,重庆400016

出　　处：《重庆医科大学学报》2016年第11期1113-1116,共4页Journal of Chongqing Medical University

基　　金：国家临床重点专科建设资助项目(编号:财社[2011]170号)

摘　　要：目的:本研究旨在收集一个特发性低促性腺激素性性腺功能减退症(idiopathic hypogonadotropic hypogonadism,IHH)的家系成员资料,通过基因检测确定其突变位点,丰富疾病突变谱。方法:对家系成员进行病史采集、生化及影像学检查。应用高通量测序技术检测先证者突变位点,Sanger测序技术对先证者及家系成员进行基因型验证。结果:该家系为近亲结婚家系,先证者为25岁女性,表现为青春期发育延迟、原发性闭经、不孕、促性腺激素及性激素水平低下,先证者妹妹及弟弟也存在明显青春期发育延迟,父母为表兄妹关系且临床表型正常。基因检测结果示先证者KISS1R基因5号外显子上,第983号碱基胞嘧啶突变为腺嘌呤(c.C983A),使第328号氨基酸丝氨酸突变为终止密码子(p.S328X),蛋白质翻译提前终止。父母为该突变位点的杂合子,妹妹为纯合子。结论:通过基因检测,发现了KISS1R基因上的一个新的致病突变c.C983A(p.S328X)。Objective：To detect the unknown mutation gene and to expand the mutation spectrum by describing a Chinese family with idiopathic hypogonadotropic hypogonadism（IHH）. Methods：Clinical information of family members were collected. Second-generation sequencing technology was used to determine the proband＇s mutation. Sanger sequencing was used to confirm proband＇s mutation results and to detect her parents and younger sister. Results：In the inbreeding family,the proband（25-year-old）showed delayed puberty,primary amenorrhea,infertility,lack of gonadotropins and other typical manifestations of IHH. The proband＇s younger brother and sister were also showed delayed puberty. The proband＇s parents are cousins and are healthy. Sequencing analysis identified a novel nonsense mutation in exon 5 of the KISS1 R gene（c.C983 A,p. S328X）. The proband and her sister were in homozygous state and her parents were in heterozygous state. Conclusion：We have identified a novel homozygous nonsense mutation in the KISS1 R gene causing IHH.

关 键 词：特发性低促性腺激素性性腺功能减退症 基因突变 无义突变 KISS1R 

分 类 号：R588.6[医药卫生—内分泌]