Shimizu Yusaku, Yoshida Kunihiro, Okano Tomomi, Ohara Shinji, Hashimoto Takao, Fukushima Yoshimitsu, Ikeda Shu-Ichi
Department of Neurology, Ina Central Hospital, 1313-1 Ina, Ina 396-8555, Japan.
Division of Clinical and Molecular Genetics, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
J Hum Genet. 2004;49(11):610-616. doi: 10.1007/s10038-004-0196-6. Epub 2004 Oct 8.
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.
对来自长野县的86个无亲缘关系的家庭进行了常染色体显性遗传性小脑共济失调（ADCA）亚型的频率研究。在长野，脊髓小脑变性（SCD）的患病率约为每10万人中22例。在ADCA家庭中，SCA6是最常见的亚型（16个家庭，19%），其次是齿状核红核苍白球路易体萎缩症（DRPLA）（9个家庭，10%）、SCA3/马查多-约瑟夫病（MJD）（3个家庭，3%）、SCA1（2个家庭，2%）和SCA2（1个家庭，1%）。未检测到SCA7、SCA12或SCA17的家庭。与日本其他地区相比，长野的SCA3/MJD患病率非常低。更有趣的是，长野遗传未确定的ADCA家庭比例（55个家庭，65%）远高于日本其他地区。这些家庭倾向于聚集在木曾、佐久和伊那等地理上受限的地区，表明奠基者效应可能是这些地区ADCA高发的原因。大多数患者临床上表现为晚发性缓慢进展的单纯小脑共济失调（ADCA III型）。然而，在36个遗传未确定的ADCA III型家庭的36名患者中，没有一人与为16q-ADCA提出的奠基者等位基因完全一致。这些结果表明，长野可能存在遗传上不同的ADCA亚型。
