J Med Genet 50:133-139 doi:10.1136/jmedgenet-2012-101406
  • Review

Role of PRRT2 in common paroxysmal neurological disorders: a gene with remarkable pleiotropy

Editor's Choice
  1. Leanne M Dibbens
  1. School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia, Adelaide, Australia
  1. Correspondence to Dr Sarah E Heron, School of Pharmacy and Medical Sciences, University of South Australia, P4-47, City East Campus, GPO Box 2471, Adelaide, SA 5001, Australia; sarah.heron{at}
  • Received 7 November 2012
  • Revised 18 December 2012
  • Accepted 20 December 2012
  • Published Online First 23 January 2013


Mutations in the gene PRRT2 encoding proline-rich transmembrane protein 2 have recently been identified as the cause of three clinical entities: benign familial infantile epilepsy (BFIE), infantile convulsions with choreoathetosis (ICCA) syndrome, and paroxysmal kinesigenic dyskinesia (PKD). Patients with ICCA have both BFIE and PKD and families with ICCA may contain individuals who exhibit all three phenotypes. These three phenotypes were all mapped by linkage analyses to the pericentromeric region of chromosome 16, and were hypothesised to have the same genetic basis due to the co-occurrence of the disorders in some families. Despite considerable effort, the gene or genes for BFIE, ICCA, and PKD were not identified for many years after the linkage region was identified. Mutations in the gene PRRT2 were identified in several Chinese families with PKD, suggesting that the gene may also be responsible for ICCA and BFIE in families linked to the chromosome 16 locus. This was demonstrated to be the case, with the majority of families with ICCA and BFIE found to have PRRT2 mutations. The vast majority of these mutations are truncating and are predicted to lead to haploinsufficiency. PRRT2 is a largely uncharacterised protein. It is expressed in the brain and has been demonstrated to interact with SNAP-25, a component of the molecular machinery involved in the release of neurotransmitters at the presynaptic membrane. Therefore, the PRRT2 protein may play a role in this process. However, the molecular mechanisms underlying the remarkable pleiotropy associated with PRRT2 mutations have still to be determined.