Abstract
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.
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Acknowledgements
The authors are deeply grateful to patients for their participation in this study and to Drs. Atsushi Inoue, Kosuke Naito (Kiso Prefectural Hospital), Hiroyuki Yahikozawa, Masashi Yamazaki, Shun’ichi Sato (Nagano Red Cross Hospital), Katsuhiko Kayanuma (Ina Central hospital), Ken’ichi Tabata, Jun Miki (Saku General Hospital), Keiko Maruyama (Suwa Red Cross Hospital), Teruaki Iwahashi (National Nagano Hospital), and Hiroshi Morita, Yo-ichi Takei (Shinshu University Hospital) for providing us with clinical information. We also thank Drs. Kinya Ishikawa, Shuta Toru, and Hidehiro Mizusawa (Department of Neurology, Tokyo Medical and Dental University) for their kind support of our research. This work was supported by grants from the Research Committee of Ataxic Disease (KY), Research on Specific Disease, the Ministry of Health, Labour, and Welfare of Japan.
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Shimizu, Y., Yoshida, K., Okano, T. et al. Regional features of autosomal-dominant cerebellar ataxia in Nagano: clinical and molecular genetic analysis of 86 families. J Hum Genet 49, 610–616 (2004). https://doi.org/10.1007/s10038-004-0196-6
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DOI: https://doi.org/10.1007/s10038-004-0196-6
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