title: Targeted genomic sequencing identifies PRRT2 mutations as a cause of paroxysmal kinesigenic choreoathetosis.
abstract: BACKGROUND
  Paroxysmal kinesigenic choreoathetosis (PKC) is characterised by recurrent and brief attacks of involuntary movement, inherited as an autosomal dominant trait with incomplete penetrance. A PKC locus has been previously mapped to the pericentromeric region of chromosome 16 (16p11.2-q12.1), but the causative gene remains unidentified.
  
  
  RESULTS
  Deep sequencing of this 30 Mb region enriched with array capture in five affected individuals from four Chinese PKC families detected two heterozygous PRRT2 insertions (c.369dupG and c.649dupC), producing frameshifts and premature stop codons (p.S124VfsX10 and p.R217PfsX8, respectively) in two different families. Sanger sequencing confirmed these two mutations and revealed a missense PRRT2 mutation (c.859G→A, p.A287T) in one of the two remaining families. This study also sequenced PRRT2 in 29 sporadic cases affected with PKC and identified mutations in 10 cases, including six with the c.649dupC mutation. Most variants were truncating mutations, consistent with loss-of-function and haploinsufficiency.
  
  
  CONCLUSIONS
  The present study identifies PRRT2 as the gene mutated in a subset of PKC, and suggests that PKC is genetically heterogeneous.
authors: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences; School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors: Jingyun
authors: J
authors: Li
authors: Xilin
authors: X
authors: Zhu
authors: Xin
authors: X
authors: Wang
authors: Wei
authors: W
authors: Sun
authors: Bing
authors: B
authors: Feng
authors: Te
authors: T
authors: Du
authors: Bei
authors: B
authors: Sun
authors: Fenghe
authors: F
authors: Niu
authors: Hua
authors: H
authors: Wei
authors: Xiaopan
authors: X
authors: Wu
authors: Lei
authors: L
authors: Dong
authors: Liping
authors: L
authors: Li
authors: Xingqiu
authors: X
authors: Cai
authors: Yuping
authors: Y
authors: Wang
authors: Ying
authors: Y
authors: Liu
mesh_terms: D002819:Chorea / Q000235:genetics*; D023061:Gene Order; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006239:Haplotypes; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C569370:PRRT2 protein, human