Nishizawa M
Department of Neurology, Jichi Medical School.
Nihon Rinsho. 1999 Apr;57(4):826-31.
Studies on clinical and molecular genetic aspects of Machado-Joseph disease (MJD) are reviewed. MJD is now regarded as the most common autosomal dominant form of ataxia. Analyses of haplotypes and an intragenic polymorphism in the MJD1 gene, however, ruled out the possibility that founder chromosome is present among worldwide MJD patients. The expanded CAG repeats become unstable during parent-offspring transmission and the mechanism is being studied. Two factors contributing to the intergenerational instability have sofar been identified: 1) paternal transmission and 2) a intragenic polymorphism flanking the CAG repeats. Single sperm analysis of MJD patients, however, revealed paradoxical contraction of the CAG repeat size in sperm. Correlations between the size of the CAG repeats and genetic anticipation, clinical manifestation and morphologic changes are also discussed.
本文综述了马查多-约瑟夫病（MJD）临床和分子遗传学方面的研究。MJD现被认为是最常见的常染色体显性共济失调类型。然而，对MJD1基因单倍型和基因内多态性的分析排除了全世界MJD患者中存在奠基者染色体的可能性。在亲子代传递过程中，扩展的CAG重复序列变得不稳定，其机制正在研究中。目前已确定导致代际不稳定的两个因素：1）父系传递；2）CAG重复序列侧翼的基因内多态性。然而，对MJD患者的单精子分析显示精子中CAG重复序列大小出现了矛盾的收缩。文中还讨论了CAG重复序列大小与遗传早现、临床表现和形态学变化之间的相关性。
