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J Med Genet 49:76-78 doi:10.1136/jmedgenet-2011-100635
  • New loci
  • Short report

Targeted genomic sequencing identifies PRRT2 mutations as a cause of paroxysmal kinesigenic choreoathetosis

Open Access
  1. Ying Liu1
  1. 1State 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
  2. 2Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
  3. 3Department of Psychiatry, Tongde Hospital of Zhejiang Province, Zhejiang, China
  4. 4Department of Neurology, Nanjing Brain Hospital, Jiangsu, China
  1. Correspondence to Professor Ying Liu, 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, 5 Dongdan 3 Tiao, Beijing 100005, China; liuyingpumc{at}yahoo.com Professor Yuping Wang, Department of Neurology, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing 100053, China; mdwangyp{at}yahoo.com.cn
  • Received 17 November 2011
  • Revised 22 November 2011
  • Accepted 23 November 2011
  • Published Online First 30 November 2011

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.

Methods/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.

Conclusion The present study identifies PRRT2 as the gene mutated in a subset of PKC, and suggests that PKC is genetically heterogeneous.

Footnotes

  • JL and XZ contributed equally to this work.

  • Funding This work was strongly supported by Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT IRT1006), the Science Fund for Creative Research Groups (30721063) and Natural Science Foundation of Beijing (7042037).

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was approved by the Ethics Committee of the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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