Matsumura R, Futamura N, Fujimoto Y, Yanagimoto S, Horikawa H, Suzumura A, Takayanagi T
Department of Neurology, Nara Medical University, Japan.
Neurology. 1997 Nov;49(5):1238-43. doi: 10.1212/wnl.49.5.1238.
Spinocerebellar ataxia type 6 (SCA6) is a newly classified autosomal-dominant cerebellar ataxia (ADCA) associated with CAG repeat expansion. We screened 111 patients with cerebellar ataxia for the SCA6 mutation. Of these, 35 patients were found to have expanded CAG repeats in the SCA6 gene, indicating that second to SCA3, SCA6 is the most common ADCA in Japan. Expanded alleles ranged from 21 to 29 repeats, whereas normal alleles had seven to 17 repeats. There was no change in the CAG repeat length during meiosis. The age at onset was inversely correlated with the repeat length. The main clinical feature of the 35 patients with SCA6 was slowly progressive cerebellar ataxia; multisystem involvement was not common. The 35 patients included nine cases without apparent family history of cerebellar ataxia. The sporadic cases had smaller CAG repeats (21 or 22 repeats) and a later age at onset (64.9 +/- 4.9 years) than the other cases with established family history. We also identified one patient who was homozygous for the SCA6 repeat expansion. The homozygote showed an earlier age of onset and more severe clinical manifestations than her sister, a heterozygote carrying an expanded allele with the same repeat length as the homozygote. This finding suggests that the dosage of the CAG repeat expansion plays an important role in phenotypic expression in SCA6.
6型脊髓小脑共济失调（SCA6）是一种新分类的常染色体显性遗传性小脑共济失调（ADCA），与CAG重复序列扩增相关。我们对111例小脑共济失调患者进行了SCA6突变筛查。其中，35例患者被发现SCA6基因中的CAG重复序列发生扩增，这表明在日本，SCA6是仅次于SCA3的第二常见的ADCA。扩增的等位基因重复次数范围为21至29次，而正常等位基因的重复次数为7至17次。减数分裂过程中CAG重复序列长度没有变化。发病年龄与重复序列长度呈负相关。35例SCA6患者的主要临床特征为缓慢进展的小脑共济失调；多系统受累并不常见。这35例患者中有9例无明显的小脑共济失调家族史。散发病例的CAG重复序列较短（21或22次重复），发病年龄较晚（64.9±4.9岁），而其他有家族史的病例则不然。我们还鉴定出1例SCA6重复序列扩增纯合子患者。该纯合子患者的发病年龄比其妹妹（一名携带与纯合子相同重复长度的扩增等位基因的杂合子）更早，临床表现更严重。这一发现表明，CAG重复序列扩增的剂量在SCA6的表型表达中起重要作用。
