Pulse Brain · Growing Health Evidence Index
Tier 3 — Observational / field trialPeer-reviewed

Landscape of pathogenic mutations in premature ovarian insufficiency

Hanni Ke, Shuyan Tang, Ting Guo, Dong Hou, Xue Jiao, Shan Li, Wei Luo, Bingying Xu, Shidou Zhao, Guangyu Li, Xiaoxi Zhang, Shuhua Xu, Lingbo Wang, Yanhua Wu, Jiucun Wang, Feng Zhang, Yingying Qin, Jin Li, Zi‐Jiang Chen

Nature Medicine · 2023

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Summary

This genetic association study sequenced 1,030 POI patients and 5,000 controls to map the molecular landscape of premature ovarian insufficiency. Researchers identified 195 pathogenic variants in known POI genes and discovered 20 novel POI-associated genes involved in gonadogenesis, meiosis, and folliculogenesis. Collectively, genetic variants explained approximately one-quarter of POI cases, with stronger genetic contribution in primary versus secondary amenorrhoea, offering improved diagnostic screening potential.

UK applicability

The findings are directly applicable to UK clinical genetics and reproductive medicine, informing diagnostic exome sequencing protocols for female infertility investigation and potentially enabling earlier identification of genetic POI aetiology in affected women. However, generalisation to UK populations requires validation in ethnically diverse UK cohorts, as the study population composition is not specified in the abstract.

Key measures

Frequency of pathogenic/likely pathogenic variants; burden of loss-of-function variants; genotype-phenotype correlation stratified by amenorrhoea type

Outcomes reported

The study identified pathogenic and likely pathogenic genetic variants in 59 known POI-causative genes and 20 novel POI-associated genes through whole-exome sequencing. Variants contributed to 242 cases (23.5%) of POI, with higher genetic contribution observed in primary amenorrhoea compared to secondary amenorrhoea.

Theme
Nutrition & health
Subject
Other / interdisciplinary
Study type
Research
Study design
Observational cohort with case-control association analysis
Source type
Peer-reviewed study
Status
Published
System type
Human clinical
DOI
10.1038/s41591-022-02194-3
Catalogue ID
SNmohdwe79-97j0lh

Topic tags

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