Two novel CACNA1A gene mutations associated with episodic ataxia type 2 and interictal dystonia.
BACKGROUND
Episodic ataxia type 2 (EA2) is an autosomal dominant condition that results from mutations in the CACNA1A gene. It is characterized by episodes of ataxia and nystagmus that typically last hours.


OBJECTIVE
To describe the clinical and genetic features of 2 unrelated patients who developed EA2 in childhood and late-onset dystonia.


METHODS
Pedigree study.


METHODS
University academic teaching hospital.


METHODS
Two unrelated patients with childhood-onset EA2 and adult-onset dystonia were identified through a neurogenetics clinic. The CACNA1A gene was screened by heteroduplex analysis and sequencing for mutations.


METHODS
Mutations in the CACNA1A gene.


RESULTS
Novel mutations in the pore-forming subunit of the P/Q-type calcium channels were found in both pedigrees. None of the family members carried an expansion of the CAG sequence that is found in the carboxy terminus of the CACNA1A gene.


CONCLUSIONS
Truncating mutations are the most common mutations to cause EA2. We have identified 2 novel truncating mutations that are associated with interictal dystonia. The dystonia is a late feature in this disease and may be a manifestation of a degenerative cerebellar process.
Spacey
Sian D
SD
Division of Neurology, Brain Research Center, University of British Columbia, Vancouver, Canada. spacey@interchange.ubc.ca
Materek
Luke A
LA
Szczygielski
Blajez I
BI
Bird
Thomas D
TD
D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D004421:Dystonia / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation; D010375:Pedigree; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D020864:Calcium Channels, N-Type
D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type