Phenotypic Spectrum of Idiopathic Hypogonadotropic Hypogonadism Patients With CHD7 Variants From a Large Chinese Cohort
Phenotypic Spectrum of Idiopathic Hypogonadotropic Hypogonadism Patients With CHD7 Variants From a Large Chinese Cohort
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来自中国大型队列的 CHD7 变异特发性低促性腺激素性功能减退症患者的表型谱
DOI：
10.1210/clinem/dgz182
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发表时间：
2020-05-01
影响因子：
5.8
通讯作者：
Men, Meichao
中科院分区：
文献类型：
--
作者：
Li, Jia-Da;Wu, Jiayu;Men, Meichao
目的：特发性低促性腺激素性腺功能减退症（IHH）和CHARGE（C，缺损; H，心脏异常; A，后鼻孔闭锁; R，生长和/或发育迟缓; G，性腺缺陷; E，耳畸形和耳聋）综合征是两种不同的发育障碍，具有性腺功能减退症和/或嗅觉受损的特征。CHD 7变体导致>60%的CHARGE综合征，与10%的IHH患者相似。在携带CHD 7变体的CHARGE患者中经常报告各种扩展的CHARGE样特征。在这项研究中，我们的目的是系统地分析诊断性CHARGE功能和扩展CHARGE样功能的患者与CHD 7 variants.Methods：罕见的测序变异（RSV）在177 IHH先证者通过外显子组测序确定CHD 7。结果：10.2%（18/177）的IHH先证者检出CHD 7变异型RSV。CHD 7变异患者的两个诊断性CHARGE特征（听力损失和耳畸形）显著增加。此外，CHD 7变体与一组扩展的CHARGE样表型显著相关，包括轻度眼部缺陷、消化不良/胃食管反流病和骨骼缺陷。我们还开发了一个预测模型，优先CHD 7基因检测IHH patients.Conclusion：CHD 7变异很少导致孤立的IHH。对受CHARGE综合征影响的器官的症状进行监测将有助于对这些患者进行适当的治疗。某些临床特征可以用于优先考虑CHD 7基因筛查。
Purpose: Idiopathic hypogonadotropic hypogonadism (IHH) and CHARGE (C, coloboma; H, heart abnormalities; A, choanal atresia, R, retardation of growth and/or development; G, gonadal defects; E, ear deformities and deafness) syndrome are 2 distinct developmental disorders sharing features of hypogonadism and/or impaired olfaction. CHD7 variants contribute to >60% CHARGE syndrome and similar to 10% IHH patients. A variety of extended CHARGE-like features are frequently reported in CHARGE patients harboring CHD7 variants. In this study, we aimed to systematically analyze the diagnostic CHARGE features and the extended CHARGE-like features in patients with IHH with CHD7 variants.Methods: Rare sequencing variants (RSVs) in CHD7 were identified through exome sequencing in 177 IHH probands. Detailed phenotyping was performed in the IHH patients harboring CHD7 variants and their available family members.Results: CHD7 RSVs were identified in 10.2% (18/177) of the IHH probands. Two diagnostic CHARGE features, hearing loss and ear deformities, were significantly enriched in patients with CHD7 variants. Furthermore, CHD7 variants were significantly associated with a panel of extended CHARGE-like phenotypes, including mild ocular defects, dyspepsia/gastroesophageal reflux disease and skeletal defects. We also developed a predictive model for prioritizing CHD7 genetic testing in IHH patients.Conclusion: CHD7 variants rarely cause isolated IHH. Surveillance of symptoms in CHARGE syndrome-affected organs will facilitate the proper treatment for these patients. Certain clinical features can be useful for prioritizing CHD7 genetic screening.