SCA6 mutation analysis in a large cohort of the Japanese patients with late-onset pure cerebellar ataxia

Yabe, Ichiro; Sasaki, Hidenao; Matsuura, Tohru; Takada, Akio; Akemi Wakisaka,; Suzuki, Yoshihiro; Fukazawa, Toshiyuki; Hamada, Takeshi; Oda, Tatsuro; Ohnishi, Akio; Tashiro, Kunio

« Previous Next »Journal of the Neurological Sciences
Volume 156, Issue 1 , Pages 89-95, 17 March 1998

SCA6 mutation analysis in a large cohort of the Japanese patients with late-onset pure cerebellar ataxia

Ichiro Yabe
- Department of Neurology, Hokkaido University School of Medicine, N-14 W-5, Kita-ku, Sapporo 060, Japan
Hidenao Sasaki
- Department of Neurology, Hokkaido University School of Medicine, N-14 W-5, Kita-ku, Sapporo 060, Japan
- Corresponding author. Tel.: +81 11 7161161, ext. 6028; fax: +81 11 7005356.
Tohru Matsuura
- Department of Neurology, Hokkaido University School of Medicine, N-14 W-5, Kita-ku, Sapporo 060, Japan
Akio Takada
- Department of Pathology, Hokkaido University School of Medicine, N-14 W-5, Kita-ku, Sapporo 060, Japan
Akemi Wakisaka
- Department of Pathology, Hokkaido University School of Medicine, N-14 W-5, Kita-ku, Sapporo 060, Japan
Yoshihiro Suzuki
- Department of Internal Medicine (III), Yamagata University School of Medicine, Yamagata, Japan
Toshiyuki Fukazawa
- Hokuyukai Neurological Hospital, Aapporo, Japan
Takeshi Hamada
- Hokuyukai Neurological Hospital, Aapporo, Japan
Tatsuro Oda
- Department of Psychiatry, Shimofusa National Sanatorium, Chiba, Japan
Akio Ohnishi
- Department of Neurology, University of Occupational and Environmental Health, Fukuoka, Japan
Kunio Tashiro
- Department of Neurology, Hokkaido University School of Medicine, N-14 W-5, Kita-ku, Sapporo 060, Japan

Received 18 August 1997; accepted 20 November 1997.

Abstract

Spinocerebellar ataxia type 6 (SCA6) is caused by small CAG repeat expansion in the gene encoding the α_1A-voltage-dependent-calcium channel subunit (CACNL1A4) on chromosome 19p13, and is a subgroup of the late-onset pure cerebellar ataxia (ADCA III). To investigate the prevalence of SCA6 in the Japanese, we analyzed this mutation in 23 families and 12 probands with ADCA III. The specificity and stability of the CAG repeat were examined in additional individuals and families with other miscellaneous dominant SCAs. The CAG expansion of SCA6 gene was exclusively observed in 12 of 23 families (52%) and 12 proband cases with ADCA III, but not in others. The CAG repeat was 21–33 in the disease-associated alleles (n=56), and 4–18 in normal alleles (n=1148). Expanded alleles were stable during transmission, and a significant inverse correlation for CAG repeat number with age at onset was noted. Our results indicate that SCA6 shares approximately half of the ADCA III in the Japanese, and that gene mutations causing the remaining, have yet to be identified.

Keywords: SCA6, Spinocerebellar degeneration, CAG repeat, Triplet repeat disorder, Ataxia, ADCA III