Clinical and molecular features of idiopathic hypogonadotropic hypogonadism in Taiwan: A single center experience
Clinical and molecular features of idiopathic hypogonadotropic hypogonadism in Taiwan: A single center experience
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DOI：
10.1016/j.jfma.2021.03.010
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发表时间：
2021-12-15
影响因子：
3.2
通讯作者：
Tung, Yi-Ching
中科院分区：
文献类型：
--
作者：
Cho, Chih-Yi;Tsai, Wen-Yu;Tung, Yi-Ching
背景资料：特发性（孤立性）低促性腺激素性性腺功能减退症（IHH）是一种罕见的疾病，可归类为卡尔曼综合征（KS）或正常性IHH（nIHH）。本研究探讨台湾病患之IHH之表型与基因型。研究方法：本研究纳入了26例不相关的IHH患者，并回顾性分析了其临床、激素和放射学表现。进行全外显子组测序（WES）以确定病因。结果：26例患者（男：女= 19：7）分为KS组（n = 11）和nIHH组（n = 15）。男孩的诊断早于女孩。15例患者存在致病性/可能致病性（P/LP）变异，突变检出率为58%。CHD 7、FGFR 1和ANOS 1是该组中最常见的遗传病因。发现2例nIHH患者具有新发SOX 11突变和Coffin-Siris综合征特征。治疗后，身高结果和第二性征明显改善。遗传学解决（GR），变异的不确定的意义（VUS）和遗传学未解决的组（GUR）之间没有明显的差异。结论：全外显子组测序在IHH患者中是有用的，我们在这项研究中确定了SOX 11基因是一个致病因素。我们描述了台湾IHH患者的临床、激素和分子特征以及治疗结果，这有助于治疗计划和进一步研究。版权所有（c）2021，台湾医学会。由爱思唯尔台湾有限公司出版。这是一个在CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/bync-nd/4.0/）。
Background: Idiopathic (isolated) hypogonadotropic hypogonadism (IHH) is a rare disease that can be classified as Kallmann syndrome (KS) or normosmic IHH (nIHH). This study investigated the phenotype and genotype of IHH in Taiwanese patients. Methods: Twenty-six unrelated IHH patients were included in this study and their clinical, hor-monal, and radiological findings were analyzed retrospectively. Whole exome sequencing (WES) was performed to identify the etiology. Results: The 26 patients (M:F = 19:7) were divided into a KS group (n = 11) anda nIHH group (n = 15). The diagnosis was earlier in boys than in girls. Fifteen patients were found to have pathogenic/likely pathogenic (P/LP) variants of IHH-associated genes, and the mutation detec-tion rate was 58%. CHD7, FGFR1, and ANOS1 were the most common genetic etiologies identi-fied in this group. Two patients with nIHH were found to have de novo SOX11 mutations and Coffin-Siris syndrome features. After treatment, the height outcomes and secondary sexual characteristics were significantly improved. There were no obvious differences between the genetically resolved (GR), variants of uncertain significance (VUS) and genetically unresolved groups (GUR). Conclusion: Whole exome sequencing is useful in patients with IHH, and we identified the SOX11 gene as a causal factor in this study. We described the clinical, hormonal, and molecular characteristics, and the treatment outcomes, of Taiwanese patients with IHH, which should aid therapeutic planning and further research. Copyright (c) 2021, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).