不同FGFR1突变与先天性低促性腺激素性性腺功能减退症的相关性  

Correlation between different FGFR1 mutations and congenital hypogonadotropic hypogonadism

作　　者：杨宇帆 王曦[1] 聂敏[1] 伍学焱[1] 茅江峰[1] YANG Yufan;WANG Xi;NIE Min;WU Xueyan;MAO Jiangfeng(Department of Endocrinology,Peking Union Medical College Hospital,CAMS&PUMC,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医学院北京协和医院内分泌科,北京100730

出　　处：《基础医学与临床》2023年第5期733-738,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(81771576,81971375);北京自然科学基金(7212080);中国医学科学院医学与健康科技创新工程2021年“揭榜挂帅”项目,中国罕见病的精准诊疗研究(2021-I2M-1-003)。

摘　　要：目的通过对成纤维细胞生长因子受体1(FGFR1)基因突变的先天性低促性腺激素性性腺功能减退症(CHH)患者多个基因进行筛查,寻找是否同时存在其他基因突变,共同导致疾病发生。方法对15例FGFR1突变CHH患者的突变来源进行验证。对其他CHH相关基因进行筛查。通过生信分析,评价这些突变基因的致病性。结果1)9例患者FGFR1突变来源于生殖表型正常的父/母(遗传突变组)。2)遗传突变组中有6例患者存在其他致病性突变,分别是PROKR2(W178S)、FGF8(T121N)、HS6ST1(P242L)、SEMA3A(R734W)、LZTR1(Q10Rfs15)和FGFR1复合杂合突变。这些突变和FGFR1突变可能一起协同作用导致CHH发生。3)6例FGFR1自发突变(自发突变组)患者中,未发现存在其他CHH相关基因致病性突变。结论来自生殖表型正常父/母的FGFR1突变,存在另一个CHH相关基因突变协同打击才导致CHH。本研究扩展了对双基因突变导致CHH的发病机制认识。Objective To investigate whether multiple gene mutations were existed to cause congenital hypogonadotropic hypogonadism(CHH),by screening genes in CHH patients with FGFR1 mutations.Methods FGFR1 mutations were identified in 15 CHH patients.Other CHH-related genes were screened in these patients.Bioinformatics software was used to analyze the pathogenicity of gene variant.Results 1)Mutations in FGFR1 were inherited from parents in 9 patients(inherited mutation group)in spite of the fact,their parents showed normal reproductive axis function.2)In the inherited mutation group,6 patients harbored another mutation including PROKR2(W178S),FGF8(T121N),HS6ST1(P242L),SEMA3A(R734W),LZTR1(Q10Rfs15)and FGFR1 compound heterozygous mutation.Multiple gene mutations may lead to CHH.3)Six patients were found to have de novo mutations in FGFR1(de novo mutation group)but not no other pathogenic CHH related gene mutations.Conclusions FGFR1 mutations inherited from parents may require another blow from CHH-related genes to cause CHH.This study expands our understanding of the pathogenesis of CHH caused by digenic mutation.

关 键 词：先天性低促性腺激素性性腺功能减退症(CHH) 成纤维细胞生长因子受体1(FGFR1) 双基因突变 

分 类 号：R585[医药卫生—内分泌]