Targeted whole exome sequencing and Drosophila modelling to unveil the molecular basis of primary ovarian insufficiency

AbstractSTUDY QUESTIONCan a targeted whole exome sequencing (WES) on a cohort of women showing a primary ovarian insufficiency (POI) phenotype at a young age, combined with a study of copy number variations, identify variants in candidate genes confirming their deleterious effect on ovarian function?SUMMARY ANSWERThis integrated approach has proved effective in identifying novel candidate genes unveiling mechanisms involved in POI pathogenesis.WHAT IS KNOWN ALREADYPOI, a condition occurring in 1% of women under 40 years of age, affects women ’s fertility leading to a premature loss of ovarian reserve. The genetic causes of POI are highly heterogeneous and several determinants contributing to its prominent oligogenic inheritance pattern still need to be elucidated.STUDY DESIGN, SIZE, DURATIONWES screening for pathogenic variants of 41 Italian women with non-syndromic primary and early secondary amenorrhoea occurring before age 25 was replicated on another 60 POI patients, including 35 French and 25 American women, to reveal statistically significant shared variants.PARTICIPANTS/MATERIALS, SETTING, METHODSThe Italian POI patients ’ DNA were processed by targeted WES including 542 RefSeq genes expressed or functioning during distinct reproductive or ovarian processes (e.g. DNA repair, meiosis, oocyte maturation, folliculogenesis and menopause). Extremely rare variants were filtered and selected by means of a Fisher Exact te st using several publicly available datasets. A cas...
Source: Human Reproduction - Category: Reproduction Medicine Source Type: research