title: [Missense mutation R1345Q in CACNA1A gene causes a new type of ataxia with episodic tremor: clinical features, genetic analysis and treatment in a familial case].
abstract: OBJECTIVE
  Mutations in CACNA1A, which encodes the P/Q-type calcium channel subunit, are responsible for at least 3 allelic diseases, namely type 2 episodic ataxia (EA-2), familial hemiplegic migraine?type-1 (FHM1), and spinocerebellar ataxia type-6?(SCA 6). Herein we present a case of ataxia with episodic tremors in a 19-year-old man with a missense mutation of CACNA1A gene and summarize the clinical features, genetic analysis and treatment in this case and in his affected family members.
  
  
  METHODS
  Physical examinations were conducted for the patient and his affected family members. DNA sample from the proband was analyzed with next-generation sequencing technology to identify the causative mutation. Sanger sequencing was used to confirm the gene mutation in the family members.
  
  
  RESULTS
  Physical examinations of the patient revealed signs of ataxia, drunken gait, and tremor of his head and body. Four other members in his family had similar but much milder symptoms. A heterozygous missense mutation in CACNA1A (NM_001127221.1 c.4034G->A, p.R1345Q, exon 25) was identified in the proband, which was confirmed in the affected family members. The proband did not respond to methazolamide treatment, but his tremor symptom was well controlled with flunarizine, a calcium channel blocker.
  
  
  CONCLUSIONS
  Based on the clinical features, mutation analysis and treatment response, we suggest that this patient with a missense CACNA1A mutation, R1345Q, has a new type of ataxia with episodic tremor other than any of EA2, FHM1, or SCA 6.
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.E-mail: jianghs@smu.edu.cn.
authors.forename: Hai-Shan
authors.initials: HS
authors.lastname: Jiang
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Wang
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Man
authors.initials: M
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Su-Yue
authors.initials: SY
authors.lastname: Pan
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Hu
mesh_terms: D001259:Ataxia / Q000235:genetics*; D015220:Calcium Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D014202:Tremor / Q000235:genetics*; D055815:Young Adult; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type