Regional features of autosomal-dominant cerebellar ataxia in Nagano: clinical and molecular genetic analysis of 86 families

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.

A −16C>T substitution in the 5′ UTR of the puratrophin-1 gene is prevalent in autosomal dominant cerebellar ataxia in Nagano

“…More importantly, the majority of families (65%) were genetically undefined; such families make up 17-50% of the ADCA families in other parts of Japan (Maruyama et al 2002;Sasaki et al 2003;Shimizu et al 2004). A common haplotype of 16q22-linked ADCA reported by Li et al (2003) was not confirmed in our series (Shimizu et al 2004).…”

“…We previously showed that the incidence of SCA, excluding MSA, was higher (22 in 100,000) in Nagano than in other parts of Japan. In 86 unrelated ADCA families from Nagano, SCA6 (19%) and DRPLA (10%) were common, while SCA3/MJD (3%), SCA1 (2%), and SCA2 (1%) were infrequent (Shimizu et al 2004). More importantly, the majority of families (65%) were genetically undefined; such families make up 17-50% of the ADCA families in other parts of Japan (Maruyama et al 2002;Sasaki et al 2003;Shimizu et al 2004).…”

“…In 86 unrelated ADCA families from Nagano, SCA6 (19%) and DRPLA (10%) were common, while SCA3/MJD (3%), SCA1 (2%), and SCA2 (1%) were infrequent (Shimizu et al 2004). More importantly, the majority of families (65%) were genetically undefined; such families make up 17-50% of the ADCA families in other parts of Japan (Maruyama et al 2002;Sasaki et al 2003;Shimizu et al 2004). A common haplotype of 16q22-linked ADCA reported by Li et al (2003) was not confirmed in our series (Shimizu et al 2004).…”

Spectrum and prevalence of autosomal dominant spinocerebellar ataxia in Hokkaido, the northern island of Japan: a study of 113 Japanese families

“…SCA3 is quite frequent in many countries with different ethnic backgrounds, such as Portugal (80%), Germany (40%), Japan (40%), and France (30%) (Storey . In the Nagano district of Japan, DRPLA was reported to be the second most frequent of the ADCA subtypes (10%) (Shimizu et al 2004). There have also been a few reports of DRPLA from Korea (Jin et al 1999), USA (Brunetti-Pierri et al 2006) and Canada (Espay et al 2006).…”

A Japanese case of SCA14 with the Gly128Asp mutation

“…Genetic testing strategy for possible ADCA was as follows. Repeat expansions at the loci for SCA1, 2, 3, 6, 7, 12, 17, and DRPLA were first screened as described elsewhere (Shimizu et al 2004). Second, a C to T substitution in the 5¢ untranslated region in the puratrophin-1 gene, a recently identified gene for 16q22.1-linked ADCA, was examined (Ishikawa et al 2005;Ohata et al 2006).…”