Matsuyama Z, Kawakami H, Maruyama H, Izumi Y, Komure O, Udaka F, Kameyama M, Nishio T, Kuroda Y, Nishimura M, Nakamura S
Third Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Hum Mol Genet. 1997 Aug;6(8):1283-7. doi: 10.1093/hmg/6.8.1283.
Spinocerebellar ataxia 6 (SCA6) is an autosomal dominant spinocerebellar degeneration caused by the expansion of the polymorphic CAG repeat in the human alpha1A voltage-dependent calcium channel subunit gene (CACNL1A4 gene). We have analyzed 60 SCA6 individuals from 39 independent SCA6 Japanese families and found that the CAG repeat length is inversely correlated with the age of onset (n = 58, r = -0.51, P < 0.0001). SCA6 chromosomes contained 21-30 repeat units, whereas normal chromosomes displayed 6-17 repeats. There was no overlap between the normal and affected CAG repeat number. The anticipation of the disease was observed clinically in all eight parent-child pairs that we examined; the mean age of onset was significantly lower (P = 0.0042) in children than in parents. However, a parent-child analysis showed the increase in the expansion of CAG repeats only in one pair and no diminution in any affected cases. This result suggests that factors other than CAG repeats may produce the clinical anticipation. A homozygotic case could not demonstrate an unequivocal gene dosage effect on the age of onset.
脊髓小脑共济失调6型（SCA6）是一种常染色体显性脊髓小脑变性疾病，由人类α1A电压依赖性钙通道亚基基因（CACNL1A4基因）中多态性CAG重复序列的扩增引起。我们分析了来自39个独立的日本SCA6家系的60名SCA6患者，发现CAG重复序列长度与发病年龄呈负相关（n = 58，r = -0.51，P < 0.0001）。SCA6染色体包含21 - 30个重复单位，而正常染色体显示6 - 17个重复。正常和受累的CAG重复数之间没有重叠。在我们检查的所有8对亲子对中临床上都观察到了疾病的遗传早现现象；儿童的平均发病年龄明显低于父母（P = 0.0042）。然而，亲子分析显示仅在一对中CAG重复序列的扩增增加，且在任何受累病例中均未减少。这一结果表明，除CAG重复序列外的其他因素可能导致临床遗传早现现象。纯合子病例未显示出对发病年龄有明确的基因剂量效应。
