Landscape of pathogenic mutations in premature ovarian insufficiency

Premature ovarian insufficiency (POI) is a major cause of female infertility due to early loss of ovarian function. POI is a heterogeneous condition, and its molecular etiology is unclear. To identify genetic variants associated with POI, here we performed whole-exome sequencing in a cohort of 1,030 patients with POI. We detected 195 pathogenic/likely pathogenic variants in 59 known POI-causative genes, accounting for 193 (18.7%) cases. Association analyses comparing the POI cohort with a control cohort of 5,000 individuals without POI identified 20 further POI-associated genes with a significantly higher burden of loss-of-function variants. Functional annotations of these novel 20 genes indicated their…

• CN
  Capital Normal University
• SU
  Shandong University
• NN
  National Natural Science Foundation of China

  Awards: 32030020, 2017YFC1001100, B13016, 32070847, 32288101, 31988101, 2017SHZDZX01, 82125014
• HU
  Huazhong University of Science and Technology
• NS
  Natural Science Foundation of Shandong Province

  Awards: ZR202105250005, ZR2022YQ69
• HE
  Higher Education Discipline Innovation Project

  Awards: 2017SHZDZX01, B13016