title: The R900S mutation in CACNA1S associated with hypokalemic periodic paralysis.
abstract: 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.
authors.affiliation: Department of Neurology, the First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ke
authors.affiliation: Department of Neurology, the First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Fangping
authors.initials: F
authors.lastname: He
authors.affiliation: Center for Genetic & Genomic Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Lingping
authors.initials: L
authors.lastname: Lu
authors.affiliation: Center for Genetic & Genomic Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.affiliation: Program in Clinical Medicine, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yajian
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Zhejiang Provincial Key Laboratory of Biometrology and Inspection & Quarantine, College of Life Sciences, China Jiliang University, Hangzhou, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Weng
authors.affiliation: BGI, Shenzhen, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.affiliation: BGI, Shenzhen, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yi
authors.affiliation: Center for Genetic & Genomic Medicine, Zhejiang University, Hangzhou, China; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA. Electronic address: mingqi@zju.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Qi
mesh_terms: D000086:Acetazolamide / Q000627:therapeutic use; D000328:Adult; D044466:Asian People; D015220:Calcium Channels / Q000235:genetics*; D020746:Calcium Channels, L-Type; D005260:Female; D006801:Humans; D020514:Hypokalemic Periodic Paralysis / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011188:Potassium / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D014223:Triamterene / Q000627:therapeutic use
chemical_list: C412223:CACNA1S protein, human; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D000086:Acetazolamide; D011188:Potassium; D014223:Triamterene
keywords: CACNA1S; Hypokalemic periodic paralysis; Muscle channelopathy; R900S mutation