| Background:Proline-rich transmembrane protein2(PRRT2) gene encodes a gene with340amino acid, the product of which is a proline-rich transmembrane protein, but its function is unknown. In2011,Wang and Chen etc was the first to clone this gene in the disease of Paroxysmal kinesigenic dyskinesias (PKD), and then it reported that PRRT2mainly contributed to benign familial infantile seizures (BFIS) and infantile convulsions with paroxysmal choreoathetosis (ICCA). More than50kinds of point mutations in PRRT2have been identified until now. However, there are some patients with PKD, BFIS, ICCA not found point mutation of PRRT2, so these patients may be hurted by unconventional mutation of PRRT2or other genes. In addition, it is reported that the mutation of PRRT2can also be found in a variety of paroxysmal disease in nervous system, such as epilepsy. Relationship between PRRT2and epilepsy need to be detected in our study.Objective:By screening point mutation and deletion mutations of PRRT2in PKD, BFIS, ICCA, we want to set up the workflow of genetic diagnosis in PKD, BFIS and ICCA. By sequencing point mutations in febrile seizures and infant idiopathic epilepsy, we want to expand PRRT2-related paroxysmal disorders. Methods:All the subjects enrolled in the study included13PKD/IC CA pedigrees and22sporadic patients,3BFIS/ICCA Pedigrees and28sporadic patients,3FS pedigrees and26sporadic patients,202infant idiopathic epilepsy patients. We conducted Sanger sequencing of PRRT2exonic and exon-intron boundary regions to check the point mutations in PKD, BFIS and ICCA, then detected deletion mutations by qPCR in patients without point mutations of PRRT2..We used Sanger sequencing of PRRT2exonic and exon-intron boundary regions to find the point mutations in infant idiopathic epilepsy.Results:Our analysis revealed two known mutations c.649dupC (p.Arg217ProfsX8) and c.649delC (pArg217GlufsX12) in PKD/ICCA8pedigrees and5sporadic patients, two exonic variants c.383C>T and c.412C>G in2sporadic patients, heterozygous deletion of PRRT2in3PKD/IC pedigrees and7sporadic patients. Our sthdy find two known mutations c.649dupC (p.Arg217ProfsX8) and c.629dupC (pAla211Serfs-X14) in3BFIS/ICCA pedigrees and2BIS sporadic patients, heterozygous deletion of PRRT2in2BIS sporadic patients. We also detected known mutations c.649dupC (p.Arg217ProfsX8) in a sporadic patients with FS.Conclusion:1. PRRT2is a major causative gene of PKD, BFIS and ICCA, and heterozygous deletion of PRRT2probably cause PKD and BFIS.2. Our sthdy detected a new point mutation c.383C>T (p.Ser128Phe) in PRRT23.PRRT2may be a causative gene of FS and probably not a common responsibility gene of infant idiopathic epilepsy. |
