Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia


Paroxysmal kinesigenic dyskinesia is the most common type of paroxysmal movement disorder and is often misdiagnosed clinically as epilepsy. Using whole-exome sequencing followed by Sanger sequencing, we identified three truncating mutations within PRRT2 (NM_145239.2) in eight Han Chinese families with histories of paroxysmal kinesigenic dyskinesia: c.514_517delTCTG (p.Ser172Argfs*3) in one family, c.649dupC (p.Arg217Profs*8) in six families and c.972delA (p.Val325Serfs*12) in one family. These truncating mutations co-segregated exactly with the disease in these families and were not observed in 1,000 control subjects of matched ancestry. PRRT2 is a newly discovered gene consisting of four exons encoding the proline-rich transmembrane protein 2, which encompasses 340 amino acids and contains two predicted transmembrane domains. PRRT2 is highly expressed in the developing nervous system, and a truncating mutation alters the subcellular localization of the PRRT2 protein. The function of PRRT2 and its role in paroxysmal kinesigenic dyskinesia should be further investigated.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: The pedigrees of the eight families affected by paroxysmal kinesigenic dyskinesia included in the present study.
Figure 2: PRRT2 protein domain structure.
Figure 3: Expression of PRRT2 in the mouse brain.
Figure 4: Truncated PPRT2 has altered cellular localization.

Accession codes




  1. Kertesz, A. Paroxysmal kinesigenic choreoathetosis. An entity within the paroxysmal choreoathetosis syndrome. Description of 10 cases, including 1 autopsied. Neurology 17, 680–690 (1967).

    Article  CAS  PubMed  Google Scholar 

  2. Bruno, M.K. et al. Clinical evaluation of idiopathic paroxysmal kinesigenic dyskinesia: new diagnostic criteria. Neurology 63, 2280–2287 (2004).

    Article  CAS  PubMed  Google Scholar 

  3. Goodenough, D.J., Fariello, R.G., Annis, B.L. & Chun, R.W. Familial and acquired paroxysmal dyskinesias. A proposed classification with delineation of clinical features. Arch. Neurol. 35, 827–831 (1978).

    Article  CAS  PubMed  Google Scholar 

  4. Tomita, H. et al. Paroxysmal kinesigenic choreoathetosis locus maps to chromosome 16p11.2-q12.1. Am. J. Hum. Genet. 65, 1688–1697 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Swoboda, K.J. et al. Paroxysmal kinesigenic dyskinesia and infantile convulsions: clinical and linkage studies. Neurology 55, 224–230 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. Bennett, L.B., Roach, E.S. & Bowcock, A.M. A locus for paroxysmal kinesigenic dyskinesia maps to human chromosome 16. Neurology 54, 125–130 (2000).

    Article  CAS  PubMed  Google Scholar 

  7. Valente, E.M. et al. A second paroxysmal kinesigenic choreoathetosis locus (EKD2) mapping on 16q13-q22.1 indicates a family of genes which give rise to paroxysmal disorders on human chromosome 16. Brain 123, 2040–2045 (2000).

    Article  PubMed  Google Scholar 

  8. Kikuchi, T. et al. Paroxysmal kinesigenic choreoathetosis (PKC): confirmation of linkage to 16p11-q21, but unsuccessful detection of mutations among 157 genes at the PKC-critical region in seven PKC families. J. Hum. Genet. 52, 334–341 (2007).

    Article  CAS  PubMed  Google Scholar 

  9. Ono, S. et al. Mutation and copy number analysis in paroxysmal kinesigenic dyskinesia families. Mov. Disord. 26, 761–763 (2011).

    Article  PubMed  Google Scholar 

  10. Ng, S.B. et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 461, 272–276 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wang, J. et al. The diploid genome sequence of an Asian individual. Nature 456, 60–65 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ng, P.C. & Henikoff, S. SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res. 31, 3812–3814 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Su, A.I. et al. A gene atlas of the mouse and human protein-encoding transcriptomes. Proc. Natl. Acad. Sci. USA 101, 6062–6067 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bhatia, K.P., Griggs, R.C. & Ptácek, L.J. Episodic movement disorders as channelopathies. Mov. Disord. 15, 429–433 (2000).

    Article  CAS  PubMed  Google Scholar 

  15. Celesia, G.G. Disorders of membrane channels or channelopathies. Clin. Neurophysiol. 112, 2–18 (2001).

    Article  CAS  PubMed  Google Scholar 

  16. Li, R. et al. SOAP2: an improved ultrafast tool for short read alignment. Bioinformatics 25, 1966–1967 (2009).

    Article  CAS  PubMed  Google Scholar 

  17. Li, R. et al. SNP detection for massively parallel whole-genome resequencing. Genome Res. 19, 1124–1132 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. McKenna, A. et al. The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kruglyak, L., Daly, M.J., Reeve-Daly, M.P. & Lander, E.S. Parametric and nonparametric linkage analysis: a unified multipoint approach. Am. J. Hum. Genet. 58, 1347–1363 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Hu, X.L. et al. Conditional deletion of NRSF in forebrain neurons accelerates epileptogenesis in the kindling model. Cereb. Cortex 21, 2158–2165 (2011).

    Article  PubMed  Google Scholar 

Download references


The authors sincerely thank the participants for their help and willingness to take part in this study. The authors also thank the Beijing Genomics Institute (BGI)-Shenzhen for assistance in the analysis of exome sequence data. This work was supported by a grant from the National Natural Science Foundation (China; 81125009 to Z.-Y.W.) and a grant from Huashan Hospital for the special professorship of Fudan University (to Z.-Y.W.) and by a key program of scientific research of Fujian Medical University (2009D064 to N.W.).

Author information

Authors and Affiliations



N.W. and Z.-Y.W. planned the project. Z.-Q.X., J.X., N.W. and Z.-Y.W. conceived of and designed the study. W.-J.C., Yu Lin, Yi Lin, S.-X.M., N.W. and Z.-Y.W. performed the sample collection. W.-J.C., Yu Lin, W.W., W.N., J.H., Y.-F.C., Q.-J.Z. and H.-F.L. performed sequence analysis. J.-F.X. and Z.-Y.W. performed linkage and haplotype analyses. Z.-Q.X., G.-H.T. and S.-L.G. performed the expression analysis. W.-J.C., Z.-Q.X., J.X., N.W. and Z.-Y.W. analyzed the data. W.-J.C., Z.-Q.X. and Z.-Y.W. wrote the manuscript, and J.X. and Z.-Y.W. revised it.

Corresponding authors

Correspondence to Ning Wang or Zhi-Ying Wu.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–3 and Supplementary Tables 1 and 2 (PDF 1391 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Chen, WJ., Lin, Y., Xiong, ZQ. et al. Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia. Nat Genet 43, 1252–1255 (2011).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing