The expansion of the CAG repeat in ataxin-2 is a frequent cause of autosomal dominant spinocerebellar ataxia
The expansion of the CAG repeat in ataxin-2 is a frequent cause of autosomal dominant spinocerebellar ataxia
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DOI：
10.1212/wnl.49.4.1009
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发表时间：
1997-10-01
期刊：
影响因子：
9.9
通讯作者：
Zoghbi, HY
中科院分区：
文献类型：
--
作者：
Lorenzetti, D;Bohlega, S;Zoghbi, HY
常染色体显性遗传性脊髓小脑共济失调（ADSCA）是一组迟发性神经退行性疾病，具有重叠的临床特征。遗传连锁研究已经确定了至少7个不同的基因座的ADSCA，允许这些疾病的遗传分类。脊髓小脑性共济失调2型（SCA2）基因定位于12号染色体，最近分离出一个导致这种疾病的基因。引起SCA2的突变是一个新基因编码区中含有的三核苷酸CAG重复序列的扩增。我们描述的SCA2重复的基因型分析结果与ADSCA谁以前被发现在SCA1，SCA3，或SCA6基因CAG重复扩增阴性的个人。已在15个独立的家庭中确定了扩展的CAG重复。在两个大的kinestra中观察到重复不稳定和预期。在我们的ADSCA激酶中发现了SCA2突变，证实了SCA2在这组疾病中的高比例。
The autosomal dominant spinocerebellar ataxias (ADSCAs) are a heterogeneous group of late-onset neurodegenerative disorders with overlapping clinical features. Genetic linkage studies have identified at least seven distinct loci for the ADSCAs, allowing the genetic classification of these disorders. The spinocerebellar ataxia type 2 (SCA2) locus was mapped to chromosome 12, and a gene responsible for this disorder was recently isolated. The mutation causing SCA2 is an expansion of a trinucleotide CAG repeat contained within the coding region of a novel gene. We describe the results of genotypic analysis for the SCA2 repeat in individuals with ADSCA who were previously found negative for CAG repeat expansions in the SCA1, SCA3, or SCA6 genes. The expanded CAG repeat has been identified in 15 independent families. Repeat instability and anticipation were observed in two large kindreds. The SCA2 mutation was found in 18% of our ADSCA kindreds, confirming the high proportion of SCA2 among this group of disorders.