Ichikawa Y
Department of Neurology, Graduate School of Medicine, University of Tokyo.
Nihon Rinsho. 1999 Apr;57(4):832-7.
Machado-Joseph disease (MJD) is a progressive neurodegenerative disease which is characterized clinically by cerebellar ataxia and variable associated symptoms; it is inherited with an autosomal dominant manner. The disease is caused by an unstable expansion of the CAG repeat in MJD1 that maps to chromosome 14q32.1. There have been reported three intragenic polymorphic sites in MJD1. One is CA 926A/CAG within the CAG repeat, the others are accompanying with amino acid changes; 318Arg(987 CGG)/Gly(GGG) and 361Stop(TA1118A)/Tyr(TAC). Haplotype analyses showed 987C-1118A is exclusively associated with MJD chromosomes and normal chromosomes carrying the larger CAG repeat in the Japanese population. These results suggested that linkage disequilibrium between the MJD and intragenic polymorphisms, and the possibility of the presence of the haplotype which is prone to expansion of the CAG repeat.
马查多-约瑟夫病（MJD）是一种进行性神经退行性疾病，临床特征为小脑共济失调及多种相关症状；它以常染色体显性方式遗传。该疾病由MJD1基因中CAG重复序列的不稳定扩增引起，MJD1基因定位于染色体14q32.1。据报道，MJD1基因存在三个基因内多态性位点。一个是CAG重复序列内的CA 926A/CAG，另外两个伴随着氨基酸变化；318Arg(987 CGG)/Gly(GGG)和361Stop(TA1118A)/Tyr(TAC)。单倍型分析表明，在日本人群中，987C-1118A仅与携带较大CAG重复序列的MJD染色体和正常染色体相关。这些结果提示MJD与基因内多态性之间存在连锁不平衡，以及存在易于CAG重复序列扩增的单倍型的可能性。
