The Genetics of Non-Syndromic Primary Ovarian Insufficiency: A Systematic Review

Several causes for primary ovarian insufficiency (POI) have been described, including iatrogenic and environmental factor, viral infections, chronic disease as well as genetic alterations. The aim of this review was to collect all the ge- netic mutations associated with non-syndromic POI. All studies, including gene screening, genome-wide study and as- sessing genetic mutations associated with POI, were included and analyzed in this systematic review. Syndromic POI and chromosomal abnormalities were not evaluated. Single gene perturbations, including genes on the X chromosome (such as BMP15, PGRMC1 and FMR1) and genes on autosomal chromosomes (such as GDF9, FIGLA, NOBOX, ESR1, FSHR and NANOS3) have a positive correlation with non-syndromic POI. Future strategies include linkage analysis of families with multiple affected members, array comparative genomic hybridization (CGH) for analysis of copy number variations, next generation sequencing technology and genome-wide data analysis. This review showed variability of the genetic factors associated with POI. These findings may help future genetic screening studies on large cohort of women.