Abstract:?Objective?To investigate the genetic etiology of a case of mental retardation complicated with epilepsy and dyskinesia by the whole exome sequencing (WES) technique, and its pathogenic mechanism.?Methods?The DNAs from peripheral blood cells of the patient and his parents were extracted. Then, the pathogenic genes of the patient were searched by the WES technique, and the pathogenic sites were further verified by Sanger sequencing. Last, the pathogenic gene was cloned by mouse cDNA, and the protein expressed by the pathogenic gene and wild type protein were compared by western blot.?Results?The WES detected a nonsense mutation of?PRRT2?gene (c.649C>T; p.R217X) in the patient, which was inherited from his mother. Sanger sequencing results were consistent with that of WES. western blot confirmed that the mutant protein of mouse Prrt2 R223X, corresponding to human PRRT2 R217X, could not be expressed normally.?Conclusion?The c.649C>T mutation of?PRRT2?gene may be the cause of mental retardation in this patient. The mutant protein PRRT2 R217X cannot be expressed normally.