Spinocerebellar ataxia type 6: CAG repeat expansion in alpha1A voltage-dependent calcium channel gene and clinical variations in Japanese population.
Autosomal dominant spinocerebellar ataxias (SCAs) are clinically and genetically a heterogeneous group of neurodegenerative disorders. Recently, mild CAG repeat expansion in the alpha1A voltage-dependent calcium channel gene has been found to be associated with a type of autosomal dominant SCA (SCA6). We analyzed 98 Japanese families with autosomal dominant SCAs, for whom CAG repeat expansions of the SCA1, SCA2, Machado-Joseph disease/SCA3, and dentatorubral-pallidoluysian atrophy genes were excluded, and 5 apparently sporadic cases of cortical cerebellar atrophy. The diagnosis of SCA6 was confirmed in 30 families (31%) comprising 47 affected individuals and 1 sporadic case. The size of expanded CAG repeats ranged from 21 to 26 repeat units and was found to be correlated inversely with age at onset. We identified 2 SCA6 patients homozygous for expanded CAG repeats, whose ages at onset were earlier than the 95% lower confidence level, suggesting the presence of a gene dosage effect of expanded CAG repeat. Ataxia is the most common initial symptom found in 45 of the 48 patients. Patients with a prolonged disease course showed other accompanying clinical features including dystonic postures, involuntary movements, and abnormalities in tendon reflexes.
Ikeuchi
T
T
Department of Neurology, Brain Research Institute, Niigata University, Japan.
Takano
H
H
Koide
R
R
Horikawa
Y
Y
Honma
Y
Y
Onishi
Y
Y
Igarashi
S
S
Tanaka
H
H
Nakao
N
N
Sahashi
K
K
Tsukagoshi
H
H
Inoue
K
K
Takahashi
H
H
Tsuji
S
S
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D015220:Calcium Channels / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D013132:Spinocerebellar Degenerations / Q000208:ethnology / Q000235:genetics*; D018911:Trinucleotide Repeats; D020864:Calcium Channels, N-Type
D015220:Calcium Channels; D017931:DNA Primers; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type