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

Nat Genet. 2011 Nov 20;43(12):1252-5. doi: 10.1038/ng.1008.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Brain / metabolism
  • Case-Control Studies
  • Chorea / genetics*
  • Exome*
  • Female
  • Frameshift Mutation*
  • Gene Components
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Linkage
  • Heredity
  • Humans
  • INDEL Mutation*
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins
  • Organ Specificity
  • Pedigree
  • Protein Structure, Tertiary
  • Sequence Analysis, DNA
  • Spinal Cord / metabolism
  • Transcription, Genetic


  • Membrane Proteins
  • Nerve Tissue Proteins
  • PRRT2 protein, human