Wang Hong-Xia, Li Hong-Fu, Liu Gong-Lu, Wen Xiao-Dan, Wu Zhi-Ying
Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040; Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, The Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
Chin Med J (Engl). 2016 May 5;129(9):1017-21. doi: 10.4103/0366-6999.180529.
Paroxysmal kinesigenic dyskinesia (PKD) is the most common subtype of paroxysmal dyskinesias and is caused by mutations in PRRT2 gene. The majority of familial PKD was identified to harbor PRRT2 mutations. However, over two-third of sporadic PKD patients did not carry anyPRRT2 mutation, suggesting an existence of additional genetic mutations or possible misdiagnosis due to clinical overlap.
A cohort of 28 Chinese patients clinically diagnosed with sporadic PKD and excluded PRRT2 mutations were recruited. Clinical features were evaluated, and all subjects were screened for MR-1, SLC2A1, and CLCN1 genes, which are the causative genes of paroxysmal nonkinesigenic dyskinesia (PNKD), paroxysmal exertion-induced dyskinesia, and myotonia congenita (MC), respectively. In addition, 200 genetically matched healthy individuals were recruited as controls.
A total of 16 genetic variants including 4 in MR-1 gene, 8 in SLC2A1 gene, and 4 in CLCN1 gene were detected. Among them, SLC2A1 c.363G>A mutation was detected in one case, and CLCN1 c.1205C>T mutation was detected in other two cases. Neither of them was found in 200 controls as well as 1000 Genomes database and ExAC database. Both mutations were predicted to be pathogenic by SIFT and PolyPhen2. The SLC2A1 c.363G>A mutation was novel.
The phenotypic overlap may lead to the difficulty in distinguishing PKD from PNKD and MC. For those PRRT2- negative PKD cases, screening of SLC2A1 and CLCN1 genes are useful in confirming the diagnosis.
发作性运动诱发性运动障碍（PKD）是发作性运动障碍最常见的亚型，由PRRT2基因突变引起。大多数家族性PKD被鉴定为携带PRRT2突变。然而，超过三分之二的散发性PKD患者未携带任何PRRT2突变，这表明存在其他基因突变或因临床症状重叠而可能导致误诊。
招募了28例临床诊断为散发性PKD且排除PRRT2突变的中国患者。评估了临床特征，并对所有受试者进行了MR-1、SLC2A1和CLCN1基因的筛查，这三个基因分别是发作性非运动诱发性运动障碍（PNKD）、发作性运动诱发性运动障碍和先天性肌强直（MC）的致病基因。此外，招募了200名基因匹配的健康个体作为对照。
共检测到16个基因变异，其中MR-1基因4个，SLC2A1基因8个，CLCN1基因4个。其中，1例检测到SLC2A1基因c.363G>A突变，另外2例检测到CLCN1基因c.1205C>T突变。在200名对照以及千人基因组数据库和ExAC数据库中均未发现这两种突变。SIFT和PolyPhen2预测这两种突变均具有致病性。SLC2A1基因c.363G>A突变是新发现的。
表型重叠可能导致区分PKD与PNKD和MC存在困难。对于那些PRRT2阴性的PKD病例，筛查SLC2A1和CLCN1基因有助于确诊。
