Endocrine Abstracts

Background: Sequencing of Primary Ovarian Insufficiency cohorts have identified variants in >100 “POI genes” in up to 50% of women but establishing pathogenicity is challenging. Early-onset POI (EO-POI; adolescents) may have a distinct genetic profile.Methods: We performed exome sequencing (Nonacus) in an EO-POI cohort. Filtering (QCI) retained variants which were 1) rare/novel (MAF<0.01%), 2) predicted pathogenic in silico, 3)...

Context: The complex genetic mechanisms underlying human ovary development can give rise to clinical phenotypes if disrupted, such as Primary Ovarian Insufficiency and Differences of Sex Development. In recent years, RNA sequencing (RNAseq) approaches have characterised ovary development in previously unparalleled detail; however, a challenge is synthesising and using these data to advance our understanding of clinical disease.Methods: We combine single-...

Background: Turner syndrome (TS) is the most common genetic cause of Primary Ovarian Insufficiency (POI). Morphological analyses of human fetal 45,X ovaries have demonstrated germ cell apoptosis by 15-20 weeks post conception (wpc). However, we do not know why POI develops mechanistically. Here, we use single-nuclei RNA sequencing (snRNA-seq) and bulk RNA sequencing to identify novel potential mechanisms of ovarian insufficiency in TS and to characterise X chromosome gene expr...