Xie Yidan, Zheng Ruizhi, Han Binbin, Yuan Huijuan, Hu Ziying
Department of Endocrine, Henan University People's Hospital, Zhengzhou, Henan 450000, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2022 Jun 10;39(6):571-575. doi: 10.3760/cma.j.cn511374-20210415-00331.
To explore clinical evaluation and genetic analysis of patients with idiopathic hypogonadotropic hypogonadism (IHH).
The clinical data and phenotypes of 22 patients with IHH diagnosed and treated in our department were reviewed and analyzed. Whole-exome sequencing (WES) and Sanger method were used for variant analysis and verification.
Among the 22 cases of IHH probands, 12 cases of Kalman syndrome (KS) and 10 cases of IHH (nIHH) with normal sense of smell. On physical examination, males showed short penis, small testicles, small or inconspicuous laryngeal knots, and a sharp voice. Mammary gland development, mammary gland dysplasia, primary amenorrhea, etc. in women. Sex hormone examination: Follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2) levels are reduced or at the lower limit of normal. There were nine missense variants of CHD7 gene in 8 patients. Based on the American College of Medical Genetics and Genomics guidelines, the c.307T>A(p.Ser103Thr), c.3143G>A(p.Gly1048Glu), c.6956G>T (p.Arg2319Leu) and c.3145A>T (p.Ser1049Cys) variants of CHD7 gene were predicted to be likely pathogenic (PS1+PP1+PM2, PM2+PM6+PP2+PP3, PM2+PM5+PM6+PP2+PP3 and PM2+PM6+PP2+PP3), the remaining 14 cases of IHH patients had negative genetic screening.
CHD7 gene variants may be related to IHH disease.
探讨特发性低促性腺激素性性腺功能减退症（IHH）患者的临床评估及基因分析。
回顾性分析我院收治的22例IHH患者的临床资料及表型。采用全外显子测序（WES）及Sanger法进行变异分析及验证。
22例IHH先证者中，12例为卡尔曼综合征（KS），10例为嗅觉正常的IHH（nIHH）。体格检查显示，男性表现为阴茎短小、睾丸小、喉结小或不明显、声音尖细。女性表现为乳腺发育、乳腺发育不良、原发性闭经等。性激素检查：促卵泡生成素（FSH）、促黄体生成素（LH）、睾酮（T）、雌二醇（E2）水平降低或处于正常下限。8例患者的CHD7基因存在9个错义变异。依据美国医学遗传学与基因组学学会指南，CHD7基因的c.307T>A（p.Ser103Thr）、c.3143G>A（p.Gly1048Glu）、c.6956G>T（p.Arg2319Leu）和c.3145A>T（p.Ser1049Cys）变异被预测为可能致病（PS1+PP1+PM2、PM2+PM6+PP2+PP3、PM2+PM5+PM6+PP2+PP3和PM2+PM6+PP2+PP3），其余14例IHH患者基因筛查为阴性。
CHD7基因变异可能与IHH疾病相关。
