Novel <it>PRRT2</it> mutation in an African-American family with paroxysmal kinesigenic dyskinesia

• Main Authors: Hedera Peter, Xiao Jianfeng, Puschmann Andreas, Momčilović Dragana, Wu Steve W, LeDoux Mark S
• Format: Article
• Language: English
• Published: BMC 2012-09-01
• Series: BMC Neurology
• Subjects: PKD; PRRT2; African-American; ICCA; Hotspot mutation
• Online Access: http://www.biomedcentral.com/1471-2377/12/93

<p>Abstract</p> <p>Background</p> <p>Recently, heterozygous mutations in <it>PRRT2</it> (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.</p> <p>Methods</p> <p>Sanger sequencing was used to analyze all four <it>PRRT2</it> exons for sequence variants in 13 probands (9 Caucasian, 1 Caucasian-Thai, 1 Vietnamese and 2 African-American) with some form of paroxysmal dyskinesia.</p> <p>Results</p> <p>One patient of mixed Caucasian-Thai background and one African-American family harbored the previously described hotspot mutation in <it>PRRT2</it> (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 <it>PRRT2</it> transcripts. All affected individuals had classic paroxysmal kinesigenic dyskinesia phenotypes.</p> <p>Conclusions</p> <p>Heterozygous <it>PRRT2</it> gene mutations also cause paroxysmal kinesigenic dyskinesia in African-Americans. The c.649dupC hotspot mutation in <it>PRRT2</it> is common across racial groups.</p>