The investigation of the genetic etiology in mental retardation and / or multiple congenital anomaly cases BY next generation sequencing technique

Mental retardation (MR) is defined as significantly lower average general intellectual function caused by the loss of all ability to affect intelligence and progress. Currently, the term "intellectual disability (ID)" is being used instead of MR. Approximately 1-3 percent of the global population has an intellectual disability. ID is more common in men than in women. ID may be isolated or may be associated with multiple congenital anomalies (MCA). In this study, eight of undiagnosed ID and/or MCA cases supposed to have genetic etiyology were analyzed by whole exome sequencing. The results revealed that three of four cases had the X-linked inheritance pattern and one of them showed the autosomal recessive pattern of inheritance. The diagnosis was established for these four cases corresponding 50 percent diagnosis rate. The mutations in these cases were found to be in IQSEC2 (p.Val900Ile), PLAG2G6 (p.Leu542Phe), AGTR2 (p.Tyr189X), FRMPD4 (p.Asp1033Asn) genes. All of the mutations identified in our patients were novel. Furthermore, the novel mutations in PMS2 and MSH2 mutations were coincidentally identified in two patients and their parents, and these genes are proposed to be reported by American College of Medical Genetics. this study is the first study in our country which aim to figure out the etiology of undiagnosed ID and/or MCA cases with next generation sequencing. The identification of genetic etiology for these kind of cases will contribute to prevent complications and provide more effective genetic counseling for affected families.