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References OMIM Gene GeneReviews HGMD HGNC
last update : 03/06/2010
Symbol SCA6
Location 19p13.2
HGNC id 10559
Name spinocerebellar ataxia 6
Corresponding gene CACNA1A
Main clinical features
  • predominant cerebellar phenotype (cebellar ataxia type I) without retinal degeneration, slowly progressive, late-onset , most frequently sporadic, with numerous oval or rod shaped aggregates in the Purkinje cells leading to their degeneration, and atrophy of the cerebellar vermis
  • may be associated with nigral loss and dopaminergic dysfunction
  • Genetic determination autosomal dominant
    Prevalence 1.59/100000
    Function/system disorder neurology
    Type disease
    Gene product
    Name calcium voltage gated channel (CACNA1A)
    Gene mutationChromosome rearrangementEffectComments
    repeat expansion   other stable expansion of the CAG repeat(20-29) in exon 47
  • mutation in the intracellular domain between s4 and s5 of repeat 3 can cause atypical nystagmus/cerebellar phenotypes, including isolated nystagmus
  • pathogenic mechanism of SCA6 involves the endolysosomal degradation pathway (PMID: 23054835))
  • lysosomal accumulation and storage of mutant within Purkinje cells is associated with toxicity, therefore decreasing the mutant load either by activating the autophagic response or by lysosomal exocytosis may be an effective therapeutic strategy for this disease (PMID: 23054835))
  • Genotype/Phenotype correlations
  • predominant cerebellar phenotype (cebellar ataxia type I) without retinal degeneration, progressive, with anticipation and triplet CAG repeat amplification in the intracellular C-terminus region of CACNA1A calcium channel, allelic to EA2