男性特发性低促性腺激素型性腺功能减退症3例致病基因分析  

Genetic Mutation Analysis of 3 Children with Idiopathic Hypogonadotropic Hypogonadism

作　　者：刘威[1] 乔洁[2] 汝颖[3] 刘炳丽[1] 韩兵[2] 吴佳君[2] 杨邵英[1] 薛丽琼[1] 宋怀东[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院分子医学中心,上海200025 [2]上海交通大学医学院附属第九人民医院内分泌代谢科,上海200011 [3]安徽医科大学附属省立医院内分泌科,合肥230001

出　　处：《实用儿科临床杂志》2011年第6期438-441,共4页Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金(81070666)

摘　　要：目的对3例特发性低促性腺激素型性腺功能减退症(IHH)患者进行致病基因检测,以探讨其可能存在的致病基因突变。方法收集临床资料和血标本,并进行详细的实验室检查,采用FUJIFILM QuickGene-610L抽提外周血白细胞DNA,针对目前5个主要的Kallmann综合征的致病基因和嗅觉正常的IHH(nIHH)致病基因[促性腺激素释放激素受体(GnRHR)基因]采用PCR扩增6个基因的全部外显子。PCR产物直接测序后,采用Auto Assemble软件比对寻找突变。结果 2例患者诊断为Kallmann综合征,1例患者诊断为nIHH;基因测序结果发现,除了在2例患者中发现了位于内分泌腺源性血管内皮生长因子受体2(PROKR2)基因上的单核苷酸多态性改变外,3例患者均无Kallmann综合征1基因(KAL1),成纤维细胞生长因子受体1(FGFR1),PROKR2和内分泌腺源性血管内皮生长因子2(PROK2),成纤维细胞生长因子8(FGF8)基因的突变,1例nIHH患者也无GnRHR基因突变。结论 IHH是一种在临床和基因水平异质性疾病,对3例IHH患者排除了目前主要致病基因的突变,提示其他基因或致病因素参与此病的发生。Objective To explore the molecular basis in 3 patients with idiopathic hypogonadotropic hypogonadism（IHH） by gene test.MethodsClinical data and blood preparation were collected and careful laboratory examinations were carried out in 3 patients with IHH.Genomic DNA was extracted by FUJIFILM QuickGene-610L from peripheral blood,and 5 most frequent genes of Kallmann syndrome at present and Gonadotropin-releasing hormone receptor（GnRHR） gene of idiopathic hypogonadotropic hypogonadism with normal olfaction（nIHH） were analyzed by amplifying all exons of these 6 genes by PCR,followed by direct PCR product-sequencing.The results of sequencing were analyzed by using Auto Assemble software to detect mutations.ResultsTwo patients were diagnosed with Kallmann syndrome and 1 patient was diagnosed with nIHH.Except for the fact that 2 single nucleortide polymorphism（SNP） sites in prokineticin receptor 2（PROKR2） gene were detected in 2 patients,no mutation was identified in Kallmann syndrome 1（KAL1）,fibroblast growth factor receptor 1（FGFR1）,PROKR2,prokineticin 2（PROK2） or fibroblast growth factor 8（FGF8） gene in these patients.Moreover,GnRHR gene mutation was not detected in the nIHH patient.ConclusionsIHH is a clinically and genetically heterogeneous disease,and the most frequent mutation genes of IHH were excluded in these 3 patients.It demonstrates that mutations in other genetic sites remain to be disclosed.J Appl Clin Pediatr,2011,26（6）： 438-441

关 键 词：特发性低促性腺激素型性腺功能减退症 嗅觉正常的特发性低促性腺激素型性腺功能减退症 KALLMANN综合征 基因突变 单核苷酸多态性 

分 类 号：R725.8[医药卫生—儿科]