title: Frequency analysis of autosomal dominant cerebellar ataxias in Japanese patients and clinical characterization of spinocerebellar ataxia type 6.
abstract: Using a molecular diagnostic approach, we investigated 101 kindreds with autosomal dominant cerebellar ataxias (ADCAs) from the central Honshu island of Japan, including spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2), Machado-Joseph disease (MJD), dentatorubral and pallidoluysian atrophy (DRPLA) and spinocerebellar ataxia type 6 (SCA6). In our unselected series, MJD was the most common type of ADCA, accounting for 33.7% followed by DRPLA (19.8%), SCA2 (5.9%) and SCA6 (5.9%). No SCA1 mutations were identified. We analysed the clinical features of six molecular confirmed SCA6 kindreds: in each family, there was an expanded allele in the alpha1A-voltage dependent calcium channel comprising between 23 and 25 CAG repeats. The mean age at onset of symptoms was 43+/-13 years. The clinical features consisted predominantly of cerebellar ataxia, dysarthria and horizontal nystagmus, which was generally consistent with ADCA type 3. However several new clinical features were found in some patients: dramatic anticipation, rapid disease progression, severe ataxia associated with action tremor or action myoclonus, and very early onset, which are not described as the classical features of ADCA type 3.
authors.affiliation: Department of Neurology, Nagoya University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Watanabe
authors.forename: F
authors.initials: F
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: M
authors.initials: M
authors.lastname: Doyu
authors.forename: T
authors.initials: T
authors.lastname: Ando
authors.forename: T
authors.initials: T
authors.lastname: Mitsuma
authors.forename: G
authors.initials: G
authors.lastname: Sobue
mesh_terms: D000328:Adult; D002524:Cerebellar Ataxia / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant; D006801:Humans; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D013132:Spinocerebellar Degenerations / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology*