Landscape of pathogenic mutations in premature ovarian insufficiency
Authors' conclusion
This study expands understanding of the genetic landscape underlying POI and presents insights that have the potential to improve the utility of diagnostic genetic screenings.
Study context
- Population
- Patients with premature ovarian insufficiency (POI)
- Participants
- 1,030 vs 5,000
- Comparison
- POI cohort vs control cohort without POI
- POIn = 1,030
- Controln = 5,000reference
- Outcome
- Pathogenic/likely pathogenic variants in known POI-causative genes
Methodological detailswhole-exome sequencing, case-control association analysis
- Whole-exome sequencing
- Case-control association analysis
Main finding
As reported in the abstract
POI
18.7%
193 of 1,030
- P/LP variants detected in 59 known POI-causative genes
- 195
- P/LP variants in known POI-causative and novel POI-associated genes, cases
- 242 (23.5%)
Observational data: associations, not effects.
Further findings
Novel POI-associated genes (burden of loss-of-function variants vs controls)
- Further POI-associated genes with significantly higher burden of loss-of-function variants
- 20
- Involved in gonadogenesis (LGR4, PRDM1), meiosis (CPEB1, KASH5, MCMDC2, MEIOSIN, NUP43, RFWD3, SHOC1, SLX4, STRA8) and folliculogenesis and ovulation (ALOX12, BMP6, H1-8, HMMR, HSD17B1, MST1R, PPM1B, ZAR1, ZP3)
Genotype-phenotype correlation
- Genetic contribution higher in primary vs secondary amenorrhea
Original publication
Landscape of pathogenic mutations in premature ovarian insufficiency. Nat Med. Published 2 February 2023. doi:10.
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