Ikeuchi T
Department of Neurology, Niigata University.
Nihon Rinsho. 1999 Apr;57(4):891-5.
Spinocerebellar ataxia type 6 (SCA6, MIM 183086) is an autosomal dominant spinocerebellar degeneration. Mild expansion of a CAG repeat in voltage-dependent Ca2+ channel alpha 1A subunit (CACNL1A) gene, which was predicted to encode a polyglutamine tract, has been identified as a causative mutation for SCA6. SCA6 is one of the common subtypes of spinocerebellar degeneration, accounting for approximately 12% in the dominantly inherited ataxias in Japan. Mean age at onset in the SCA6 patients is 52 years, which is much later than those reported for other autosomal dominant ataxias including SCA1, SCA2, Machado-Joseph disease, and dentatorubral-pallidoluysian atrophy. Anticipation in SCA6 is quite mild. The size of expanded CAG repeats ranged 21 to 26 repeats and was found to be correlated inversely with age at onset in patients with SCA6. Ataxia is most common and cardinal clinical features in SCA6. Patients with a prolonged clinical course, however, show other accompanying clinical features including dystonic postures, involuntary movements, and abnormalities in tendon reflexes. Investigations of the mechanisms of neuronal death in the cerebellum, in particular relation to the impaired function of the voltage-dependent Ca2+ channel and the toxic effects of expanded polyglutamine tracts, will be indispensable for the development of therapeutic measures for SCA6.
6型脊髓小脑共济失调（SCA6，MIM 183086）是一种常染色体显性脊髓小脑变性疾病。电压依赖性Ca2+通道α1A亚基（CACNL1A）基因中的CAG重复序列轻度扩增，该基因预计编码一个多聚谷氨酰胺序列，已被确定为SCA6的致病突变。SCA6是脊髓小脑变性的常见亚型之一，在日本常染色体显性遗传性共济失调中约占12%。SCA6患者的平均发病年龄为52岁，这比包括SCA1、SCA2、马查多-约瑟夫病和齿状核红核苍白球路易体萎缩症在内的其他常染色体显性共济失调的报道发病年龄要晚得多。SCA6的遗传早现现象相当轻微。扩增后的CAG重复序列长度在21至26个重复之间，并且发现与SCA6患者的发病年龄呈负相关。共济失调是SCA6最常见和主要的临床特征。然而，病程较长的患者会出现其他伴随的临床特征，包括肌张力障碍姿势、不自主运动和腱反射异常。研究小脑神经元死亡的机制，特别是与电压依赖性Ca2+通道功能受损和扩增的多聚谷氨酰胺序列的毒性作用之间的关系，对于开发SCA6的治疗措施将是必不可少的。
