Zoghbi H Y, Orr H T
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Semin Cell Biol. 1995 Feb;6(1):29-35. doi: 10.1016/1043-4682(95)90012-8.
Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disorder characterized by ataxia, dysarthria and progressive bulbar dysfunction. The SCA 1 gene which maps to the short arm of chromosome 6 has been isolated using a positional cloning approach. The SCA1 transcript is 10660 bases and encodes a novel protein, ataxin-1, with a predicted molecular weight of 87 kDa. Expansion of a CAG repeat localized near the amino terminus of ataxin-1 has been found to be the mutational mechanism in SCA1. This CAG repeat is highly polymorphic with normal alleles containing 6-39 repeats. Individuals affected with SCA1 have one normal allele and one expanded allele containing 40-81 repeats. The size of the repeat correlates inversely with the age of onset of symptoms and the severity of disease. The repeat is a continuous CAG repeat tract on SCA1 chromosomes whereas in > or = 98% of normal alleles one or more CAT interruptions break the CAG repeat tracts into two tracts containing less than 18 repeats each. This suggests that loss of CAT interruptions within the SCA1 CAG repeat on normal chromosomes leads to triplet instability.
1型脊髓小脑共济失调（SCA1）是一种常染色体显性遗传的神经退行性疾病，其特征为共济失调、构音障碍和进行性延髓功能障碍。利用定位克隆方法已分离出定位于6号染色体短臂上的SCA1基因。SCA1转录本有10660个碱基，编码一种新蛋白ataxin-1，预测分子量为87 kDa。已发现ataxin-1氨基末端附近的CAG重复序列扩增是SCA1的突变机制。该CAG重复序列高度多态，正常等位基因含有6至39个重复序列。患SCA1的个体有一个正常等位基因和一个含有40至81个重复序列的扩增等位基因。重复序列的长度与症状发作年龄及疾病严重程度呈负相关。该重复序列在SCA1染色体上是连续的CAG重复片段，而在≥98%的正常等位基因中，一个或多个CAT中断将CAG重复片段分成两个各含少于18个重复序列的片段。这表明正常染色体上SCA1 CAG重复序列中CAT中断的缺失会导致三联体不稳定。
