Ueno S, Kondoh K, Kotani Y, Komure O, Kuno S, Kawai J, Hazama F, Sano A
Department of Neuropsychiatry, Ehime University School of Medicine, Japan.
Hum Mol Genet. 1995 Apr;4(4):663-6. doi: 10.1093/hmg/4.4.663.
An unstable expansion of CAG repeat in the coding region of the DRPLA gene on chromosome 12p is the mutation specific for hereditary dentatorubral-pallidoluysian atrophy (DRPLA). We studied the CAG expansion in brain and other tissues from six unrelated DRPLA patients. The CAG repeat lengths showed distinct differences between tissues. The sizes of the CAG expansion in various regions of the brain except the cerebellum were generally larger by several repeats than in other peripheral tissues. Brain samples showed greater variation of the expansion compared with other tissues, but neither the size of the CAG expansion nor the degree of CAG repeat variation parallels the detailed findings of neuropathological involvement. We conclude that somatic instabilities of the CAG repeat cause tissue variability of the CAG repeat size in DRPLA but other region or cell type-specific factors would be involved to explain the selectivity of cell damage in DRPLA.
位于12号染色体短臂上的齿状核红核苍白球路易体萎缩症（DRPLA）相关基因DRPLA编码区的CAG重复序列不稳定扩增是遗传性齿状核红核苍白球路易体萎缩症的特异性突变。我们研究了6例无亲缘关系的DRPLA患者脑及其他组织中的CAG扩增情况。CAG重复长度在不同组织间存在明显差异。除小脑外，脑内各区域CAG扩增的大小通常比其他外周组织多几个重复序列。与其他组织相比，脑样本的扩增变异更大，但CAG扩增的大小及CAG重复变异程度均与神经病理学受累的详细表现不平行。我们得出结论，CAG重复序列的体细胞不稳定性导致了DRPLA中CAG重复序列大小的组织变异性，但其他区域或细胞类型特异性因素也参与其中，以解释DRPLA中细胞损伤的选择性。
