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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 detect the causative genes of 3 cases of idiopathic hypogonadotropic hypogonadism (IHH) in order to investigate the possible mutation of causative gene. Methods Clinical data and blood samples were collected and subjected to a detailed laboratory examination. Peripheral blood leukocyte DNA was extracted from FUJIFILM QuickGene-610L for the pathogenesis of the five major Kallmann syndromes and normoxia-induced IHH (nIHH) Disease Gene Gonadotropin-Releasing Hormone Receptor (GnRHR) Genes All the six exons of the gene were amplified by PCR. After PCR products were sequenced directly, the mutations were searched using the Auto Assemble software. Results Two patients were diagnosed as Kallmann syndrome and one patient was diagnosed as nIHH. The gene sequencing results showed that in addition to the mononuclear nuclear localization of the endocrine-derived vascular endothelial growth factor receptor 2 (PROKR2) gene in two patients The Kallmann syndrome 1 (KAL1), fibroblast growth factor receptor 1 (FGFR1), PROKR2 and endocrine glandular vascular endothelial growth factor 2 (PROK2) Fibroblast growth factor 8 (FGF8) gene mutations in 1 patient nIHH nor GnRHR gene mutation. Conclusion IHH is a heterogeneous disease at the clinical and genetic level. Three IHH patients were excluded from the current major pathogenic mutations, suggesting that other genes or pathogenic factors involved in the disease.