Regional features of autosomal-dominant cerebellar ataxia in Nagano: clinical and molecular genetic analysis of 86 families.
The frequency of autosomal-dominant cerebellar ataxia (ADCA) subtypes was examined in 86 unrelated families originating from Nagano prefecture. In Nagano, the prevalence of spinocerebellar degeneration (SCD) was approximately 22 per 100,000 population. Among ADCA families, SCA6 was the most prevalent subtype (16 families, 19%), followed by DRPLA (nine families, 10%), SCA3/MJD (three families, 3%), SCA1 (two families, 2%), and SCA2 (one family, 1%). No families with SCA7, SCA12, or SCA17 were detected. Compared with other districts in Japan, the prevalence of SCA3/MJD was very low in Nagano. More interestingly, the ratio of genetically undetermined ADCA families was much higher in Nagano (55 families, 65%) than in other districts in Japan. These families tended to accumulate in geographically restricted areas such as Kiso, Saku, and Ina, indicating that the founder effect might be responsible for the high frequency of ADCA in these areas. Most patients clinically showed slowly progressive pure cerebellar ataxia of late-onset (ADCA III). In the case of 36 patients from 36 genetically undetermined ADCA III families, however, no one was completely consistent with the founder allele proposed for 16q-ADCA. These results indicate that there might be genetically distinct ADCA subtypes in Nagano.
Department of Neurology, Ina Central Hospital, 1313-1 Ina, Ina 396-8555, Japan.
Yusaku
Y
Shimizu
Division of Clinical and Molecular Genetics, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto 390-8621, Japan. kyoshida@hsp.md.shinshu-u.ac.jp.
Kunihiro
K
Yoshida
Third Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
Tomomi
T
Okano
Department of Neurology, Chushin Matsumoto Hospital, 811 Toyooka, Kotobuki, Matsumoto 399-0021, Japan.
Shinji
S
Ohara
Third Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
Takao
T
Hashimoto
Division of Clinical and Molecular Genetics, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
Yoshimitsu
Y
Fukushima
Third Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
Shu-Ichi
SI
Ikeda
D002524:Cerebellar Ataxia / Q000453:epidemiology* / Q000235:genetics*; D018703:Founder Effect; D005787:Gene Frequency; D005843:Geography; D006801:Humans; D007564:Japan / Q000453:epidemiology; D018895:Microsatellite Repeats / Q000235:genetics; D015995:Prevalence; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics