Novel PRRT2 mutation in an African-American family with paroxysmal kinesigenic dyskinesia
- Equal contributors
1 Department of Neurology, Vanderbilt University, Nashville, TN, USA
2 Departments of Neurology, and Anatomy and Neurobiology, University of Tennessee Health Science Center, 855 Monroe Avenue, Suite 415 Link Building, Memphis, TN, 38163, USA
3 Department of Neurology, Skåne University Hospital and Department of Neurology, Lund University, Lund, Sweden
4 Clinic for Child Neurology and Psychiatry, Medical Faculty University of Belgrade, Belgrade, Serbia
5 Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA
BMC Neurology 2012, 12:93 doi:10.1186/1471-2377-12-93Published: 18 September 2012
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.
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.
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.
Heterozygous PRRT2 gene mutations also cause paroxysmal kinesigenic dyskinesia in African-Americans. The c.649dupC hotspot mutation in PRRT2 is common across racial groups.