特发性低促性腺激素性腺功能低下患者NR5A1基因突变分析  

Mutation analysis of NR5A1 gene in children with idiopathic hypogonadotropic hypogonadism

作　　者：胡思翠[1] 应艳琴[1] 叶娟[1] 付溪[1] 黄姗[1] 宁琴[1] 罗小平[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院儿科遗传代谢内分泌,武汉430030

出　　处：《中华内分泌代谢杂志》2015年第11期956-960,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：卫生部临床重点学科建设项目（201002006）

摘　　要：目的 研究特发性低促性腺激素性腺功能低下（idiopathic hypogonadotropic hypogonadism,IHH）患者NR5A1基因新的突变位点.方法 收集病例组IHH患者61例,该组患者核型正常,头颅MRI扫描正常,同时排除其他内分泌疾病,正常对照组100名.提取两组实验对象外周血白细胞DNA,分别设计NR5A1基因2～7号外显子引物,聚合酶链式反应扩增其编码序列和剪接位点,采用双脱氧末段终止法测序.将测序结果与正常人基因组进行比对,同时对患者进行家系调查,收集临床资料,并对阳性患者基因型和临床表型进行分析.结果 61例IHH患者中6例患者出现了NR5A1基因的碱基改变.通过对100个种族及年龄匹配的对照组进行分析,没有发现NR5A1基因突变位点.结论 病例组NR5A1基因检测出1种有意义的碱基改变,该突变可能与核型正常同时肾上腺功能正常的IHH男性患者发病有关.Objective To study the NR5A1 gene mutation in patients with idiopathic hypogonadotropic hypogonadism（IHH）, and to find the new mutation point.Methods Sixty-one IHH patients and 100 normal control subjects were collected and genomic DNA was extracted from blood samples.These patients were with normal karyotype and no abnormality was discovered in magnetic resonance imaging （MRI） scan of the pituitary.Other endocrine diseases were also excluded.The 2-7 exons and splice-sites of NR5A1 gene were amplified with polymerase chain reaction.DNA of the coding sequence and splice-sites of NR5A 1 were sequenced by double deoxidizing terminal end sequencing method in 61 IHH and 100 normal control subjects.The results of sequencing were compared with their corresponding sequence data.61 IHH kindreds were investigated and the clinical data of these patients were collected.Finally, the phenotype and genotype positive cases were analyzed.Results Six patients carried NR5A1 gene mutational sites in 61 cases of IHH.Analysis of sequencing results from 100 age and ethnicity matched control subjects did not show any of these novel changes.Conclusions One mutation in NR5A1 gene may affect protein structure and function, which should be considered in male IHH patients with normal karyotype and without insufficiency of adrenal function.

关 键 词：特发性低促性腺激素性腺功能低下 NR5A1 基因突变 

分 类 号：R588[医药卫生—内分泌]