Cannella Milena, Maglione Vittorio, Martino Tiziana, Simonelli Maria, Ragona Giuseppe, Squitieri Ferdinando
Neurogenetics Unit IRCCS Neuromed, Pozzilli (IS), Italy.
Am J Med Genet B Neuropsychiatr Genet. 2005 Feb 5;133B(1):127-30. doi: 10.1002/ajmg.b.30125.
The analysis of somatic CAG triplet variation in lymphoblastoid cell lines from subjects carrying alleles of intermediate length (IA(33CAG) and IA(34CAG)) in Huntington disease (HD) gene disclosed instability in the DNA of the person, from whom a new expansion mutation of 45 triplets originated. The triplet size increased after about 30 passages in cell cultures in lymphoblasts with the IA(34) genotype. Lymphoblasts may provide an appropriate model for studying repeat instability in subjects with poly(CAG) repeat disorders. HD shows somatic, in addition to germ-line instability, highlighting the propensity to somatic CAG variation in human cells even with repeat numbers under the expanded edge. Factors potentially cis acting with the mutation, other than those reported in this study (CCG polymorphic stretch, the deletion of the glutamic acid residue at position 2642 and the 4-codon segment between CAG and CCG polymorphisms), should be searched for and analyzed.
对携带亨廷顿舞蹈病（HD）基因中等长度等位基因（IA(33CAG)和IA(34CAG)）的受试者的淋巴母细胞系中的体细胞CAG三联体变异进行分析后发现，在DNA中存在不稳定性，而一个新的45个三联体的扩展突变正是源自该个体。在具有IA(34)基因型的淋巴母细胞中，经过约30次细胞培养传代后，三联体大小增加。淋巴母细胞可能为研究聚（CAG）重复序列疾病患者的重复序列不稳定性提供合适的模型。HD除了生殖系不稳定性外还表现出体细胞不稳定性，这突出了即使重复序列数量在扩展边界以下，人类细胞中体细胞CAG变异的倾向。除了本研究中报道的那些因素（CCG多态性延伸、第2642位谷氨酸残基的缺失以及CAG和CCG多态性之间的4密码子片段）外，还应寻找和分析可能与该突变顺式作用的其他因素。
