Novel missense variant of CIITA contributing to endometriosis

Research question What are the novel pathogenic variants leading to endometriosis? Design A Chinese family, in which three female offspring were diagnosed with ovarian endometriosis by pathological biopsy and the mother had ovarian cysts, were recruited to this study, plus another 111 unrelated endometriosis patients. Whole-exome sequencing was performed on the affected offspring and the parents of the family. Sanger sequencing was used to screen all the coding regions of candidate genes. Scratch wound assays, transwell migration and invasion assays were used to determine whether the mutation could affect cell migration and invasion. Results A novel missense variant in the CIITA gene (NM_001286402;c.C1949G;p.Ala650Gly) was identified in three affected sisters by exome sequencing, which was inherited from their mother, who had a suspected diagnosis of ovarian endometriosis. This variant was absent from all public databases. Another two rare missense variants of CIITA (c.1031G>T;p.Arg344Leu and c.1535T>C;p.Leu512Pro) were identified in two unrelated endometriosis patients. The scratch wound and transwell assays showed that the mutation c.C1949G;p.Ala650Gly significantly (P = 0.0307; P = 0.0162; P = 0.0117, respectively) affected cell migration and invasion ability. Conclusions The present study demonstrates that CIITA variants may contribute to the development of endometriosis.