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Abstract：
BACKGROUND: Idiopathic hypogonadotropic hypogonadism (IHH) is a rare congenital or acquired genetic disorder caused by gonadotropin-releasing hormone (GnRH) deficiency. IHH patients are divided into two major groups, hyposmic or anosmic IHH (Kallmann syndrome) and normosmic IHH (nIHH), according to whether their sense of smell is intact. Here we report a case of novel compound heterozygous mutations in the GNRH1 gene in a 15-year-old male with nIHH.
METHODS: The patient presented typical clinical symptoms of delayed testicular development, with testosterone < 3.5 mmol/L and reduced gonadotropin (follicle-stimulating hormone, luteinizing hormone) levels. Two heterozygous variants of the GNRH1 gene were detected, nonsense variant 1: c.85G > T:p.G29* and variant 2: c.1A > G:p.M1V, which disrupted the start codon.
CONCLUSIONS: Two GNRH1 mutations responsible for nIHH are identified in this study. Our findings extend the mutational spectrum of GNRH1 by revealing novel causative mutations of nIHH.
METHODS: The patient presented typical clinical symptoms of delayed testicular development, with testosterone < 3.5 mmol/L and reduced gonadotropin (follicle-stimulating hormone, luteinizing hormone) levels. Two heterozygous variants of the GNRH1 gene were detected, nonsense variant 1: c.85G > T:p.G29* and variant 2: c.1A > G:p.M1V, which disrupted the start codon.
CONCLUSIONS: Two GNRH1 mutations responsible for nIHH are identified in this study. Our findings extend the mutational spectrum of GNRH1 by revealing novel causative mutations of nIHH.
摘要：
背景：特发性低促性腺激素性腺功能减退症（IHH）是一种由促性腺激素释放激素（GnRH）缺乏引起的罕见的先天性或获得性遗传性疾病。IHH患者分为两大类，IHH（卡尔曼综合征）和正常IHH（nIHH），根据他们的嗅觉是否完好。在这里，我们报告了一例15岁男性nIHH的GNRH1基因中新型复合杂合突变的病例。
方法：患者出现典型的睾丸发育迟缓的临床症状，睾酮<3.5mmol/L和促性腺激素（促卵泡激素，黄体生成素）水平。检测到GNRH1基因的两个杂合变体，废话变体1：c.85G>T：p。G29*和变体2：c.1A>G：p。M1V,破坏了起始密码子。
结论：在这项研究中发现了两个负责nIHH的GNRH1突变。我们的发现通过揭示nIHH的新型致病突变来扩展GNRH1的突变谱。
方法：患者出现典型的睾丸发育迟缓的临床症状，睾酮<3.5mmol/L和促性腺激素（促卵泡激素，黄体生成素）水平。检测到GNRH1基因的两个杂合变体，废话变体1：c.85G>T：p。G29*和变体2：c.1A>G：p。M1V,破坏了起始密码子。
结论：在这项研究中发现了两个负责nIHH的GNRH1突变。我们的发现通过揭示nIHH的新型致病突变来扩展GNRH1的突变谱。
