Homozygous variants in CDC23 cause female infertility characterized by oocyte maturation defects

In this study, we identified two homozygous missense variants (c.986A  >  G, p.Y329C and c.988C >  T, p.R330C) inCDC23 that are responsible for female infertility characterized by oocyte maturation defects in three infertile individuals. CDC23 (cell division cycle 23) is one of the core subunits of the APC/C. In vitro experiments showed that the variant c.986A  >  G (p.Y329C) led to a decrease in CDC23 protein level and the variant c.988C >  T (p.R330C) changed the localization of CDC23 in HeLa cells and mouse oocytes. In vivo studies showed thatCdc23Y329C/Y329C mice successfully mimicked the patients ’ phenotype by causing low expression of CDC23 and APC4 and the accumulation of securin and cyclin B1 in oocytes. AZ3146 treatment was able to rescue the phenotype. Taken together, our findings reveal the important roles of CDC23 in human oocyte maturation and provide a new genetic marker for fema le infertility.
Source: Human Genetics - Category: Genetics & Stem Cells Source Type: research