Department of Neurology, Vanderbilt University, Nashville, TN, USA.
BMC Neurol. 2012 Sep 18;12:93. doi: 10.1186/1471-2377-12-93.
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.R217Pfs8). 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.
最近，PRRT2（16p11.2）杂合突变已在中、日、白种人群的发作性运动诱发性运动障碍患者中被发现。此前的工作将一个发作性运动诱发性运动障碍的基因座定位于一个非洲裔美国家系的 16p11.2-q11.2 染色体上。
对 13 名具有某种形式发作性运动障碍的先证者（9 名白种人、1 名白种-泰国人、1 名越南人和 2 名非洲裔美国人）的所有 4 个 PRRT2 外显子进行 Sanger 测序，以分析序列变异。
一名混血白种-泰国背景的患者和一个非洲裔美国家系携带有先前描述的 PRRT2（c.649dupC，p.R217Pfs8）热点突变。另一个非洲裔美国家系则发现了一个新的突变（c.776dupG，p.E260）。这两种变异都可能通过突变 PRRT2 转录本的无意义介导的衰变导致功能丧失。所有受影响的个体均具有典型的发作性运动诱发性运动障碍表型。
杂合性 PRRT2 基因突变也会导致非洲裔美国人发生发作性运动诱发性运动障碍。PRRT2 中的 c.649dupC 热点突变在不同种族群体中普遍存在。
