Mutations in Associated With Premature Ovarian Insufficiency in a Chinese Population.

Premature ovarian insufficiency (POI) is one of the most common reproductive endocrinological causes of infertility in women of child-bearing age. The purpose of this study was to identify gene mutations in Chinese patients with POI and to investigate the underlying mechanism. A total of 113 patients with idiopathic POI and 100 healthy controls were recruited for the analysis of variants. Based on the identification of common mutations in the , wild-type and mutant plasmids were constructed and transfected into HEK293 cells. Luciferase reporter genes were used to determine the effect of wild-type and mutant genotypes on the transcriptional activity of its downstream targets, the zona pellucida glycoprotein genes , and . Chromatin immunoprecipitation was used to determine the level of binding between wild-type and mutant with the , and promoters. Three different mutations were identified in four patients with POI. Two patients carried the mutation c.11C>A (p.A4E), and the other two patients, respectively, carried the mutations c.625G>A (p.V209I) and c.84C>A (p.D28E). The luciferase reporter assay indicated that , and transcriptional activities were significantly reduced in individuals with mutations. Chromatin immunoprecipitation indicated that the mutation significantly decreased binding with the , and promoters. mutation affects gene transcriptional regulation of its downstream target genes , and , highlighting a new candidate genetic factor that causes POI. Our study demonstrates that has a regulatory effect on reproduction-specific genes, thereby providing a basis for elucidating the specific regulatory mechanism of in germ cell growth and development.