Scholarlink

<p>Congenital hypogonadotropic hypogonadism (CHH) is a group of rare genetic disorders, encompassing Kallmann syndrome (KS) and normosmic isolated hypogonadotropic hypogonadism (nIHH). The clinical characteristics and genetic architecture of CHH remain unclear in East Asian populations. This study aimed to investigate the clinical characteristics and genetic spectrum of CHH in Korea. This study included 85 patients with CHH from 81 unrelated families (48 with KS, 32 with nIHH, and 5 prepubertal children with anosmia). Genetic testing consisted of Sanger sequencing for select CHH genes or next-generation sequencing approaches including targeted gene panel sequencing, whole-exome sequencing, or whole-genome sequencing. The median age at diagnosis was 16.0&#xa0;years (range, 3&#xa0;months–33&#xa0;years). Among 67 male patients, 49 (73.1%) had a history of micropenis, 21 (31.3%) had cryptorchidism, and one (1.5%) had hypospadias. Among 39 patients with KS and two prepubertal children with anosmia who underwent brain MRI, 29 (70.7%) exhibited olfactory bulb agenesis or hypoplasia. A molecular diagnosis was established in 28 of 81 probands (34.6%), including structural variants (n = 4, 4.9%). Five novel variants were detected in <i>FGFR1</i>, <i>GNRH1</i>, and <i>PROKR2</i>. <i>FGFR1</i> was the most common causative gene (10/81, 12.3%), followed by <i>ANOS1</i> (8/81, 9.9%), and <i>CHD7</i> (7/81, 8.6%). This study expands the genetic complexity and phenotypic heterogeneity of CHH in the Korean population. The identification of novel variants and structural variations highlights the importance of comprehensive genetic evaluation in patients with CHH.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Comprehensive genetic analysis defines the genetic architecture and phenotypic spectrum of Korean patients with congenital hypogonadotropic hypogonadism

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月30日

查看全文
  • Dohyung Kim,
  • Ja Hye Kim,
  • Soojin Hwang,
  • Gu-Hwan Kim,
  • Jin-Ho Choi

摘要

Congenital hypogonadotropic hypogonadism (CHH) is a group of rare genetic disorders, encompassing Kallmann syndrome (KS) and normosmic isolated hypogonadotropic hypogonadism (nIHH). The clinical characteristics and genetic architecture of CHH remain unclear in East Asian populations. This study aimed to investigate the clinical characteristics and genetic spectrum of CHH in Korea. This study included 85 patients with CHH from 81 unrelated families (48 with KS, 32 with nIHH, and 5 prepubertal children with anosmia). Genetic testing consisted of Sanger sequencing for select CHH genes or next-generation sequencing approaches including targeted gene panel sequencing, whole-exome sequencing, or whole-genome sequencing. The median age at diagnosis was 16.0 years (range, 3 months–33 years). Among 67 male patients, 49 (73.1%) had a history of micropenis, 21 (31.3%) had cryptorchidism, and one (1.5%) had hypospadias. Among 39 patients with KS and two prepubertal children with anosmia who underwent brain MRI, 29 (70.7%) exhibited olfactory bulb agenesis or hypoplasia. A molecular diagnosis was established in 28 of 81 probands (34.6%), including structural variants (n = 4, 4.9%). Five novel variants were detected in FGFR1, GNRH1, and PROKR2. FGFR1 was the most common causative gene (10/81, 12.3%), followed by ANOS1 (8/81, 9.9%), and CHD7 (7/81, 8.6%). This study expands the genetic complexity and phenotypic heterogeneity of CHH in the Korean population. The identification of novel variants and structural variations highlights the importance of comprehensive genetic evaluation in patients with CHH.