• Chih-Yi Cho, Wen-Yu Tsai, Cheng-Ting Lee, Shih-Yao Liu, Shu-Yuan Huang, Yin-Hsiu Chien, Wuh-Liang Hwu, Ni-Chung Lee, and Yi-Ching Tung.
• Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
• J Formos Med Assoc. 2022 Jan 1; 121 (1 Pt 1): 218226218-226.

BackgroundIdiopathic (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.MethodsTwenty-six unrelated IHH patients were included in this study and their clinical, hormonal, and radiological findings were analyzed retrospectively. Whole exome sequencing (WES) was performed to identify the etiology.ResultsThe 26 patients (M:F = 19:7) were divided into a KS group (n = 11) and a 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 detection rate was 58%. CHD7, FGFR1, and ANOS1 were the most common genetic etiologies identified 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).ConclusionWhole 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 © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.

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