Novel PRRT2 mutation in an African-American family with paroxysmal kinesigenic dyskinesia

BMC Neurol. 2012 Sep 18:12:93. doi: 10.1186/1471-2377-12-93.

Abstract

Background: Recently, heterozygous mutations in PRRT2 (Chr 16p11.2) have been identified in Han Chinese, Japanese and Caucasians with paroxysmal kinesigenic dyskinesia. In previous work, a paroxysmal kinesigenic dyskinesia locus was mapped to Chr 16p11.2 - q11.2 in a multiplex African-American family.

Methods: Sanger sequencing was used to analyze all four PRRT2 exons for sequence variants in 13 probands (9 Caucasian, 1 Caucasian-Thai, 1 Vietnamese and 2 African-American) with some form of paroxysmal dyskinesia.

Results: One patient of mixed Caucasian-Thai background and one African-American family harbored the previously described hotspot mutation in PRRT2 (c.649dupC, p.R217Pfs*8). Another African-American family was found to have a novel mutation (c.776dupG, p.E260*). Both of these variants are likely to cause loss-of-function via nonsense-mediated decay of mutant PRRT2 transcripts. All affected individuals had classic paroxysmal kinesigenic dyskinesia phenotypes.

Conclusions: Heterozygous PRRT2 gene mutations also cause paroxysmal kinesigenic dyskinesia in African-Americans. The c.649dupC hotspot mutation in PRRT2 is common across racial groups.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Black or African American
  • Chorea / ethnology
  • Chorea / genetics*
  • Dystonia
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Young Adult

Substances

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

Supplementary concepts

  • Familial paroxysmal dystonia