The role of the SCA2 trinucleotide repeat expansion in 89 autosomal dominant cerebellar ataxia families - Frequency, clinical and genetic correlates
The role of the SCA2 trinucleotide repeat expansion in 89 autosomal dominant cerebellar ataxia families - Frequency, clinical and genetic correlates
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DOI：
10.1093/brain/121.3.459
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发表时间：
1998-03-01
期刊：
影响因子：
14.5
通讯作者：
Wood, NW
中科院分区：
文献类型：
--
作者：
Giunti, P;Sabbadini, G;Wood, NW
脊髓小脑性共济失调2型（SCA2）是由染色体12q上的ataxin 2基因编码区域的三核苷酸（GAG）扩增引起的。89例常染色体显性小脑性共济失调（ADCA） I型、II型和II型，以及47例特发性晚发性小脑性共济失调（ILOCA）孤立病例进行了该突变分析。在38个具有ADCA I表型的家族中，有31个家族发现了SCA2突变，但在ADCA II、ADCA III或ILOCA家族中没有发现SCA2突变，证实了这种突变的特异性。具有三种已知突变（SCAI， -2或-3）的ADCA I患者的临床比较突出了组间的显着差异；SCA2患者往往病程更长，慢速扫视频率更高，肌腱反射下降。然而，这些神经症状也出现在未发现SCA2突变的ADCA I家族中，说明了直接基因检测的重要性。SCA2家庭来自不同的地理和种族背景。然而，单倍型分析未能显示出创始突变的证据，即使在来自相同地理起源的家庭中也是如此。正常等位基因的CAG重复数为17 ~ 30，病理等位基因的CAG重复数为35 ~ 51。与其他由不稳定的三核苷酸重复引起的疾病类似，重复次数与发病年龄之间存在显著的负相关，并且在传递给后代时，重复长度的父本不稳定性明显更高。SCA2突变在ADCA I患者中最为常见，占40%，而SCAI和SCA3分别占35%和15%。
The spinocerebellar ataxia type 2 (SCA2) is caused by a trinucleotide (GAG) expansion in the coding region of the ataxin 2 gene on chromosome 12q. 89 families with autosomal dominant cerebellar ataxia (ADCA) types I, II and Ill, and 47 isolated cases with idiopathic late onset cerebellar ataxia (ILOCA), were analysed for this mutation. The identification of the SCA2 mutation in 31 out of 38 families with the ADCA I phenotype, but in none of those with ADCA II ADCA III or ILOCA confirms the specificity of this mutation. A clinical comparison of the ADCA I patients with the three known mutations (SCAI, -2 or -3) highlights significant differences between the groups; SCA2 patients tended to have a longer disease duration, a higher frequency of slow saccades and depressed tendon reflexes. However, these neurological signs were also seen in an ADCA I family in which the SCA2 mutation was not identified illustrating the importance of a direct genetic test. The SCA2 families were from different geographical and ethnic backgrounds. However, haplotype analysis failed to show evidence of a founder mutation, even in families from the same geographical origin. The range of normal alleles varied from 17 to 30 CAG repeats and from 35 to 51 repeats for the pathological alleles. Similar to the other diseases caused by unstable trinucleotide repeats, a significant inverse correlation has been found between the number of repeats and age of onset, and there is a significantly higher paternal instability of repeat length on transmission to offspring. The SCA2 mutation is the most frequent amongst ADCA I patients, accounting for 40%, compared with SCAI and SCA3 which account for 35% and 15%, respectively.