Department of Endocrinology, Xi'an Central Hospital, No. 161 Xiwu Road, Xi'an, 710003, Shaanxi, China.
Medical School of Yan'an University, Yan'an, 716000, Shaanxi, China.
BMC Endocr Disord. 2023 Oct 5;23(1):213. doi: 10.1186/s12902-023-01455-7.
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.
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.
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.
特发性低促性腺激素性性腺功能减退症（IHH）是一种由促性腺激素释放激素（GnRH）缺乏引起的罕见先天性或获得性遗传疾病。根据嗅觉是否完整，IHH 患者分为两大主要群体，即嗅觉减退或嗅觉缺失性 IHH（卡尔曼综合征）和嗅觉正常性 IHH（nIHH）。在这里，我们报告了一例 15 岁男性 nIHH 患者中 GnRH1 基因的新型复合杂合突变。
该患者出现典型的睾丸发育延迟临床症状，睾酮<3.5mmol/L，促性腺激素（卵泡刺激素、黄体生成素）水平降低。检测到 GnRH1 基因的两个杂合变异，无义变异 1：c.85G>T:p.G29*和变异 2：c.1A>G:p.M1V，破坏了起始密码子。
本研究鉴定了导致 nIHH 的两个 GnRH1 突变。我们的发现通过揭示 nIHH 的新致病突变，扩展了 GnRH1 的突变谱。
