Deleterious variants in intolerant genes reveal new candidates for self-limited delayed puberty
Authors' conclusion
These findings suggest that SLDP involves both monogenic and polygenic mechanisms, with novel candidate genes contributing to its genetic basis. The association of INHBB with pubertal timing underscores its potential role in SLDP pathophysiology.
Study context
- Population
- Children with self-limited delayed puberty (SLDP), most presenting with short stature
- Participants
- 71 children
- Comparison
- SLDP patients vs gnomAD v2.0 controls
- SLDPn = 71
- Outcome
- Candidate gene variants in SLDP
Methodological detailswhole-exome sequencing, burden test vs gnomAD v2.0 controls, UK Biobank gene-phenotype analysis
- Whole-exome sequencing
- Burden test vs gnomAD v2.0 controls
- UK Biobank gene-phenotype analysis
Main finding
As reported in the abstract
High-impact variants identified in 19 candidate genes
14
Moderate-impact variants identified in 19 candidate genes
7
Candidate genes with variants significantly enriched in cases vs controls in burden test (GPS1, INHBB, SP3, NAMPT, ARID3B, NASP, FNBP1, PRDM2)
8
Further findings
UK Biobank gene-phenotype association
- INHBB additionally linked to delayed menarche
Variants in genes previously associated with growth or pubertal disorders
- Pathogenic variants (CDK13, GDF5, ANRKD11)
- 3
- Likely pathogenic variants (TYMP, DPF2, KMT2C, TP63, MC3R, GHSR)
- 6
Original publication
Deleterious variants in intolerant genes reveal new candidates for self-limited delayed puberty. Eur J Endocrinol. Published 7 April 2025. doi:10.
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