The pathophysiology of primary ovarian insufficiency (POI) is not well elucidated. Many candidate genetic aberrations are on the X-chromosome; on the contrary, many genetic perturbations are also on the autosomes. The aim of this review is to summarize the knowledge of genetic aberrations on autosomes from chromosomal rearrangement, gene abnormality, genome-wide association studies and epigenetics.
Searches of electronic databases were performed. Articles and abstracts relevant to POI and genetic studies associated with autosomes were summarized in this interpretive literature review.
Various genetic aberrations located on the autosomes were found. These abnormalities are from chromosomal rearrangement, which might disrupt the critical region on chromosome loci or disturbance of the meiosis process. Specific gene aberrations are also identified. The genes that have functions in ovarian development, folliculogenesis, and steroidogenesis on autosomes are proposed to be involved from gene association studies. Gene-to-gene interaction or epistasis also might play a role in POI occurrence. Recently, genetic techniques to study the whole genome have emerged. Although no specific conclusion has been made, the studies using genome-wide association to find the specific aberration throughout the genome in POI have been published. Epigenetic mechanisms might also take part in the pathogenesis of POI.
The considerably complex process of POI is still not well understood. Further research is needed for gene functional validation studies to confirm the contribution of genes in POI, or additional genome-wide association studies using novel clustered regularly interspaced short palindromic repeat/Cas9 technique might make these mechanisms more comprehensible.