Ke Qing, He Fangping, Lu Lingping, Yu Ping, Jiang Yajian, Weng Chen, Huang Hui, Yi Xin, Qi Ming
Department of Neurology, the First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China.
Center for Genetic & Genomic Medicine, Zhejiang University, Hangzhou, China.
Neuromuscul Disord. 2015 Dec;25(12):955-8. doi: 10.1016/j.nmd.2015.09.006. Epub 2015 Sep 9.
Primary hypokalemic periodic paralysis is an autosomal dominant skeletal muscle channelopathy. In the present study, we investigated the genotype and phenotype of a Chinese hypokalemic periodic paralysis family. We used whole-exome next-generation sequencing to identify a mutation in the calcium channel, voltage-dependent, L type, alpha subunit gene (CACNA1S), R900S, which is a rare mutation associated with hypokalemic periodic paralysis. We first present a clinical description of hypokalemic periodic paralysis patients harboring CACNA1SR900S mutations: they were non-responsive to acetazolamide, but combined treatment with triamterene and potassium supplements decreased the frequency of muscle weakness attacks. All male carriers of the R900S mutation experienced such attacks, but all three female carriers were asymptomatic. This study provides further evidence for the phenotypic variation and pharmacogenomics of hypokalemic periodic paralysis.
原发性低钾性周期性麻痹是一种常染色体显性遗传性骨骼肌离子通道病。在本研究中，我们调查了一个中国低钾性周期性麻痹家系的基因型和表型。我们使用全外显子组二代测序，在L型电压依赖性钙通道α1亚基基因（CACNA1S）中鉴定出一个R900S突变，这是一种与低钾性周期性麻痹相关的罕见突变。我们首先对携带CACNA1S R900S突变的低钾性周期性麻痹患者进行了临床描述：他们对乙酰唑胺无反应，但氨苯蝶啶和补钾联合治疗可降低肌无力发作的频率。所有R900S突变的男性携带者都经历过此类发作，但三名女性携带者均无症状。本研究为低钾性周期性麻痹的表型变异和药物基因组学提供了进一步的证据。
