Comprehensive Molecular Studies in 88 Japanese Patients With Congenital Hypogonadotropic Hypogonadism
Authors' conclusion
The results support the notion that CHH occurs not only as a monogenic disorder but also as an oligogenic/multifactorial disorder, and suggest the involvement of ZNF462, SEMA4D, and CDH2 variants in the development of CHH.
Study context
- Population
- Japanese patients with congenital hypogonadotropic hypogonadism (CHH)
- Participants
- 88 patients
- Outcome
- Pathogenic/likely pathogenic variants
Methodological detailsgene panel analysis, whole-exome sequencing
- Gene panel analysis
- Whole-exome sequencing
Main finding
As reported in the abstract
- Pathogenic/likely pathogenic variants identified
- 27
- Patients with variants via gene panel analysis (GPA) (all 88 patients)
- 30
- Patients with variants via whole-exome sequencing (WES) (58 patients without obvious variants on GPA)
- 4
- ANOS1
- 6 variants in 7 patients
- CHD7
- 3 variants in 3 patients
- FGFR1
- 14 variants in 15 patients
- PROKR2
- 2 variants in 8 patients
- SOX10
- 1 variant in 1 patient
- ZNF462 (hitherto unrecognized)
- 1 variant in 1 patient
- Patients with 2 variants
- 1
Further findings
Potentially CHH-related variants
- Genes with potentially CHH-related variants, incl. SEMA4D and CDH2
- 12
Oligogenicity and rare variants per individual in 41 CHH-related genes
- Frequency of oligogenicity significantly higher and number of rare variants per individual significantly larger in 54 CHH patients without pathogenic/likely pathogenic variants than in 100 controls
Original publication
Comprehensive Molecular Studies in 88 Japanese Patients With Congenital Hypogonadotropic Hypogonadism. J Clin Endocrinol Metab. Published 3 October 2025. doi:10.
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