Takano H, Onodera O, Takahashi H, Igarashi S, Yamada M, Oyake M, Ikeuchi T, Koide R, Tanaka H, Iwabuchi K, Tsuji S
Department of Neurology, Brain Research Institute, Niigata University, Japan.
Am J Hum Genet. 1996 Jun;58(6):1212-22.
Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disease caused by unstable expansion of a CAG repeat in the DRPLA gene. We performed detailed quantitative analysis of the size and the size distribution (range) of the expanded CAG repeats in various regions of the CNS of eight autopsied patients with DRPLA. Expanded alleles (AE) showed considerable variations in size, as well as in range, depending on the region of the CNS, whereas normal alleles did not show such variations, which indicates the occurrence of somatic mosaicism of AE in the CNS. The AE in the cerebellar cortex were consistently smaller by two to five repeat units than those in the cerebellar white matter. Moreover, the AE in the cerebral cortex were smaller by one to four repeat units than those in the cerebral white matter. These results suggest that the smaller AE in the cerebellar and cerebral cortices represent those of neuronal cells. The ranges of the AE in the cerebral cortex, cerebral white matter, and cerebellar white matter showed considerable variation ranging from 9 to 23 repeat units, whereas those in the cerebellar cortex showed little variance and were approximately 7 repeat units. The ranges of the AE in the cerebral cortex, cerebral white matter, and cerebellar white matter were much broader in patients with higher ages at death than they were in patients with lower ages at death, raising the possibility that the range of AE increases with time, as the result of mitotic instability of AE.
齿状核红核苍白球路易体萎缩症（DRPLA）是一种常染色体显性神经退行性疾病，由DRPLA基因中CAG重复序列的不稳定扩增引起。我们对8例经尸检确诊的DRPLA患者中枢神经系统各区域中扩增的CAG重复序列的大小及大小分布（范围）进行了详细的定量分析。扩增等位基因（AE）的大小及范围存在显著差异，这取决于中枢神经系统的区域，而正常等位基因则未表现出此类差异，这表明中枢神经系统中存在AE的体细胞镶嵌现象。小脑皮质中的AE始终比小脑白质中的AE小2至5个重复单位。此外，大脑皮质中的AE比大脑白质中的AE小1至4个重复单位。这些结果表明，小脑和大脑皮质中较小的AE代表神经元细胞的AE。大脑皮质、大脑白质和小脑白质中AE的范围显示出相当大的差异，为9至23个重复单位，而小脑皮质中的差异较小，约为7个重复单位。与死亡年龄较小的患者相比，死亡年龄较大的患者大脑皮质、大脑白质和小脑白质中AE的范围要宽得多，这增加了AE范围随时间增加的可能性，这是AE有丝分裂不稳定性的结果。
