PDF(Pubmed)
Abstract：
Since 1991, several genetic disorders caused by unstable trinucleotide repeats (TNRs) have been identified, collectively referred to as triplet repeat diseases (TREDs). They share a common mutation mechanism: the expansion of repeats (dynamic mutations) due to the propensity of repeated sequences to form unusual DNA structures during replication. TREDs are characterized as neurodegenerative diseases or complex syndromes with significant neurological components. Spinocerebellar ataxia type 17 (SCA17) falls into the former category and is caused by the expansion of mixed CAA/CAG repeats in the TBP gene. To date, a five-unit organization of this region [(CAG)3 (CAA)3] [(CAG)n] [CAA CAG CAA] [(CAG)n] [CAA CAG], with expansion in the second [(CAG)n] unit being the most common, has been proposed. In this study, we propose an alternative organization scheme for the repeats. A search of the PubMed database was conducted to identify articles reporting both the number and composition of GAC/CAA repeats in TBP alleles. Nineteen reports were selected. The sequences of all identified CAG/CAA repeats in the TBP locus, including 67 cases (probands and b relatives), were analyzed in terms of their repetition structure and stability in inheritance, if possible. Based on the analysis of three units [(CAG)3 (CAA)2] [CAA (CAG)n CAA CAG] [CAA (CAG)n CAA CAG], the organization of repeats is proposed. Detailed analysis of the CAG/CAA repeat structure, not just the number of repeats, in TBP-expanded alleles should be performed, as it may have a prognostic value in the prediction of stability/instability during transmission and the possible anticipation of the disease.
摘要：
自1991年以来，已经发现了几种由不稳定的三核苷酸重复（TNR）引起的遗传疾病，统称为三联重复疾病（TREDs）。它们具有共同的突变机制:由于重复序列在复制期间形成不寻常的DNA结构的倾向,重复序列的扩增(动态突变)。TRED的特征是神经退行性疾病或具有显著神经成分的复杂综合征。脊髓小脑共济失调17型（SCA17）属于前一类，是由TBP基因中混合的CAA/CAG重复序列扩展引起的。迄今为止,该地区的五个单位组织[（CAG）3（CAA）3][（CAG）n][CAACAGCAA][（CAG）n][CAACAG]，在第二[(CAG)n]单元的扩展是最常见的，已被提议。在这项研究中,我们提出了一种重复的替代组织方案。进行PubMed数据库的搜索以鉴定报道TBP等位基因中GAC/CAA重复的数量和组成的文章。选择了19份报告。TBP基因座中所有确定的CAG/CAA重复序列，包括67例(先证者和b亲属)，从它们的重复结构和继承稳定性方面进行了分析，如果可能的话。基于三个单元[(CAG)3(CAA)2][CAA(CAG)nCAACAG][CAA(CAG)nCAACAG]的分析,提出了重复的组织。详细分析了CAG/CAA重复结构,不仅仅是重复的次数，在TBP扩增的等位基因应该进行，因为它可能在预测传播过程中的稳定性/不稳定性和可能的疾病预测中具有预后价值。
