两个FSHR基因新突变导致的卵巢抵抗综合征研究  

Study of two Chinese families affected with resistant ovarian syndrome resulted from novel mutations of FSHR gene

作　　者：李汶[1,2] 何文斌[1,2] 周立花[1] 胡晓 李双飞 龚斐[1,2] 谭跃球[1,2] 

机构地区：[1]中南大学生殖与干细胞工程研究所,长沙410078 [2]中信湘雅生殖与遗传专科医院,长沙410078

出　　处：《中华医学遗传学杂志》2017年第2期196-199,共4页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金（81471432）

摘　　要：目的探讨两个高促性腺激素闭经同时窦状卵泡数目正常家系的遗传学病因，为遗传咨询及生育指导提供依据。方法应用PCR—Sanger测序的方法对2个高促性腺激素闭经家系促性腺激素受体基因（FsHR和LHCGR）进行检测，在找到可疑致病突变的情况下进行家系分析，并对该可疑突变进行生物信息学分析，预测其致病性。结果家系1和家系2先证者FSHR基因分别存在尚未报道的c．419delA（P．Lysl40Argfs’16）纯合突变和12．1510C〉T（P．Pr0504Ser）纯合突变。通过家系分析及生物信息学分析，该2个突变均为致病突变的可能性大，文献回顾这两个家系患者均为卵巢抵抗综合征而非卵巢早衰。结论发现两个卵巢抵抗综合征家系的FSHR基因新突变，丰富了FSHR基因突变谱，同时为家系遗传咨询和生育指导提供了依据。Objective To explore the genetic etiology for two Chinese families affected with hypergonadotropie amenorrhea and normal number of antral follicles. Methods Peripheral venous blood samples were collected from the families for the extraction of genomic DNA. Mutations of FSHR and LHCGR genes were screened using PCR and Sanger sequencing. Suspected pathogenic mutations were verified in other members of the families. Bioinformatics software and NCBI were used to analyze the pathogenicity of the mutations. Results Two previously unreported homozygous mutations, c. 419delA and c. 1510C^T of the FSHR gene were found in the probands of family Ⅰ and Ⅱ , respectively. Pedigree and bioinformatics analysis suggested that both mutations were pathogenic. Literature review suggested that both families were affected with resistant ovary syndrome rather than premature ovarian failure. Conclusion Two novel mutations of the FSHR gene have been identified, which have enriched the spectrum of FSHR gene mutations and provided a basis for genetic counseling and direction for reproduction.

关 键 词：高促性腺激素闭经 FSHR基因 LHCGR基因 卵巢抵抗综合征 卵巢早衰 

分 类 号：R440[医药卫生—诊断学] R711.75[医药卫生—临床医学]