Clinical and molecular features of spinocerebellar ataxia type 6.
The mutation involved in spinocerebellar ataxia type 6 (SCA6) is a small CAG expansion in the alpha-1A subunit of the voltage-dependent calcium channel gene. We looked for this mutation in 91 families with autosomal-dominant cerebellar ataxias and found that SCA6 is a minor locus in our series (2%) and is rare in France (1%). Furthermore, we did not detect the SCA6 mutation on 146 sporadic cases with isolated cerebellar ataxia or olivopontocerebellar atrophy. The normal and expanded alleles ranged from 4 to 15 and 22 to 28 CAG repeats, respectively, and age at onset was correlated to CAG repeat length (r = -0.87). In contrast with other SCA, the expanded allele was stable during transmission. Clinically, SCA6 patients (n = 12) presented with moderate to severe cerebellar ataxia with a lower frequency of associated signs compared with other SCA and a mean age at onset of 45 +/- 14 years (range, 24 to 67). MRI showed extensive cerebellar atrophy but not of the brainstem or cerebral cortex.
Stevanin
G
G
INSERM U289, Hôpital de la Salpêtrière, Paris, France.
Dürr
A
A
David
G
G
Didierjean
O
O
Cancel
G
G
Rivaud
S
S
Tourbah
A
A
Warter
J M
JM
Agid
Y
Y
Brice
A
A
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D013132:Spinocerebellar Degenerations / Q000175:diagnosis* / Q000235:genetics*; D018911:Trinucleotide Repeats