Connexion

GENATLAS PHENOTYPE

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)

Mechanism(s)

Gene mutation	Chromosome rearrangement	Effect	Comments

repeat expansion		other	stable expansion of the CAG repeat(20-29) in exon 47

Remark(s)

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