title: Novel loss-of-function PRRT2 mutation causes paroxysmal kinesigenic dyskinesia in a Han Chinese family.
abstract: BACKGROUND
  Mutations in proline-rich transmembrane protein 2 (PRRT2) are a cause of paroxysmal kinesigenic dyskinesia (PKD). In this study, we investigated the PRRT2 gene mutation in a Chinese Han family with PKD and study the pathogenesis of the mutation with PRRT2 gene.
  
  
  METHODS
  Peripheral venous blood was taken from the family members. Sanger sequencing was used for novel mutation sequencing. For the pathogenesis with the novel mutation was analyzed by bioinformatics, real-time PCR, subcellular localization and Western blot.
  
  
  RESULTS
  The Sanger sequencing showed a novel mutation, c.186-187delGC, a deletion mutation, in exon 2 of the PRRT2 gene, the frameshift mutation generated a truncated protein that was stably expressed in transfected Human embryonic kidney (HEK) 293 cells. A subcellular localization assay in COS-7 cells with GFP-tagged protein showed nuclear localization for the mutant protein while the wild-type protein was localized in membranes. Co-transfection of HEK293 cells with wild-type and mutant expression plasmids cells did not influence mRNA or protein expression from the wild-type plasmid.
  
  
  CONCLUSIONS
  Our findings demonstrated that the c.186-187delGC mutation resulted in a truncated protein from the PRRT2 gene to involve in PKD pathogenesis with haploinsufficiency. The results extend the mutation spectrum of the PRRT2 gene and provide a new example for studying the pathogenesis of the mutated PRRT2 gene.
authors.forename: Zhisong
authors.initials: Z
authors.lastname: Ji
authors.forename: Quanxi
authors.initials: Q
authors.lastname: Su
authors.forename: Lingling
authors.initials: L
authors.lastname: Hu
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.forename: Cuixian
authors.initials: C
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Deparment of Medical Genetics, School of Basic Medicine Sciences, Southern Medical University, Guangzhou, China. xiongfu@smu.edu.cn.
authors.forename: Fu
authors.initials: F
authors.lastname: Xiong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D015153:Blotting, Western; D002819:Chorea / Q000235:genetics*; D004252:DNA Mutational Analysis; D004421:Dystonia; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C569370:PRRT2 protein, human