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New loci
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Targeted genomic sequencing identifies PRRT2 mutations as a cause of paroxysmal kinesigenic choreoathetosis
  1. Jingyun Li1,
  2. Xilin Zhu1,
  3. Xin Wang1,
  4. Wei Sun2,
  5. Bing Feng3,
  6. Te Du1,
  7. Bei Sun1,
  8. Fenghe Niu1,
  9. Hua Wei2,
  10. Xiaopan Wu1,
  11. Lei Dong1,
  12. Liping Li2,
  13. Xingqiu Cai4,
  14. Yuping Wang2,
  15. 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

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.

  • Paroxysmal kinesigenic choreoathetosis
  • targeted genomic sequencing
  • PRRT2 mutations
  • mutations
  • complex traits
  • epilepsy and seizures
  • clinical genetics
  • molecular genetics
  • movement disorders (other than parkinsons)
  • neurosciences
  • nutrition and metabolism
  • genetics
  • oncology
  • liver disease
  • cancer: gastric
  • linkage

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

https://doi.org/10.1136/jmedgenet-2011-100635

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    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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