Mutations in PRRT2 responsible for paroxysmal kinesigenic dyskinesias also cause benign familial infantile convulsions

J Hum Genet. 2012 May;57(5):338-41. doi: 10.1038/jhg.2012.23. Epub 2012 Mar 8.

Abstract

Paroxysmal kinesigenic dyskinesia (PKD (MIM128000)) is a neurological disorder characterized by recurrent attacks of involuntary movements. Benign familial infantile convulsion (BFIC) is also one of a neurological disorder characterized by clusters of epileptic seizures. The BFIC1 (MIM601764), BFIC2 (MIM605751) and BFIC4 (MIM612627) loci have been mapped to chromosome 19q, 16p and 1p, respectively, while BFIC3 (MIM607745) is caused by mutations in SCN2A on chromosome 2q24. Furthermore, patients with BFIC have been observed in a family concurrently with PKD. Both PKD and BFIC2 are heritable paroxysmal disorders and map to the same region on chromosome 16. Recently, the causative gene of PKD, the protein-rich transmembrane protein 2 (PRRT2), has been detected using whole-exome sequencing. We performed mutation analysis of PRRT2 by direct sequencing in 81 members of 17 families containing 15 PKD families and two BFIC families. Direct sequencing revealed that two mutations, c.649dupC and c.748C>T, were detected in all members of the PKD and BFIC families. Our results suggest that BFIC2 is caused by a truncated mutation that also causes PKD. Thus, PKD and BFIC2 are genetically identical and may cause convulsions and involuntary movements via a similar mechanism.

MeSH terms

  • Asian People / genetics
  • Chorea / genetics*
  • DNA Mutational Analysis
  • Epilepsy, Benign Neonatal / genetics*
  • Family
  • Humans
  • Membrane Proteins / genetics*
  • Mutation*
  • Nerve Tissue Proteins / genetics*
  • Pedigree

Substances

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