A Tiered Approach to Exome Sequencing Analysis in Early-Onset Primary Ovarian Insufficiency
Authors' conclusion
The genetic basis of EO-POI is complex and affected genes span ovarian developmental processes from fetal life to adulthood. Establishing the pathogenicity of individual heterozygous variants can be challenging. However, some women have clear monogenic causes, particularly in familial POI with autosomal recessive inheritance. Others have potential polygenic causes. We describe novel candidate POI genes warranting further exploration.
Study context
- Population
- Young women with early-onset POI (<25 years) attending a specialist reproductive unit
- Participants
- 149 women
- Exposure
- Familial vs Sporadic
- Familialn = 31
- Sporadicn = 118
- Outcome
- Category 1 or 2 variants identified
Methodological detailsexome sequencing, tiered variant categorisation, single specialist reproductive unit
- Exome sequencing
- Tiered variant categorisation
- Single specialist reproductive unit
Main finding
As reported in the abstract
- Category 1 or 2 variants in 74 different genes
- 127
- Heterozygous
- 30.9%
- Homozygous
- 9.4%
- Polygenic
- 21.8%
Observational data: associations, not effects.
Further findings
Sporadic early-onset primary ovarian insufficiency (EO-POI) by variant category
- Category 1
- 21.2% (n = 25)
- Category 2
- 42.4% (n = 50)
Novel POI candidate genes (Category 3)
- PCIF1, DND1, MEF2A, MMS22L, RXFP3, C4orf33 and ARRB1
Original publication
A Tiered Approach to Exome Sequencing Analysis in Early-Onset Primary Ovarian Insufficiency. J Clin Endocrinol Metab. Published 25 February 2025. doi:10.
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