Maruyama H, Nakamura S, Matsuyama Z, Sakai T, Doyu M, Sobue G, Seto M, Tsujihata M, Oh-i T, Nishio T
Third Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Hum Mol Genet. 1995 May;4(5):807-12. doi: 10.1093/hmg/4.5.807.
Machado--Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration mapped to chromosome 14q32.1. The CAG expansions of the MJD1 gene was identified as the cause of the disease. We have analyzed 90 MJD individuals from 62 independent MJD families and found that the MJD1 repeat length is inversely correlated with the age of onset (r = -0.87). The MJD chromosomes contained 61-84 repeat units, whereas normal chromosomes displayed 14-34 repeats. In the normal chromosomes, 14 repeat units were the most common and the shortest. In association with the clinical anticipation of the disease, a parent--child analysis showed the unidirectional expansion of CAG repeats and no case of diminution in the affected family. The differences in CAG repeat length between parent and child and between siblings are greater in paternal transmission than in maternal transmission. Detailed analysis revealed that a large degree of expansion was associated with a shorter length of MJD1 gene in paternal transmission. On the other hand, the increments of increase were similar for shorter and longer expansion in maternal transmission. Among the three clinical subtypes, type I of MJD, with dystonia, showed a larger degree of expansion in CAG repeats of the gene and younger ages of onset than the other types.
马查多-约瑟夫病（MJD）是一种常染色体显性遗传性脊髓小脑变性疾病，定位于染色体14q32.1。MJD1基因的CAG重复序列扩增被确定为该病的病因。我们分析了来自62个独立MJD家族的90例MJD患者，发现MJD1重复序列长度与发病年龄呈负相关（r = -0.87）。MJD染色体含有61 - 84个重复单位，而正常染色体显示14 - 34个重复。在正常染色体中，14个重复单位最为常见且最短。与该疾病的临床遗传早现现象相关，亲子分析显示CAG重复序列单向扩增，且在受累家族中无减少情况。亲子之间以及兄弟姐妹之间CAG重复长度的差异在父系遗传中比在母系遗传中更大。详细分析表明，在父系遗传中，较大程度的扩增与MJD1基因较短的长度相关。另一方面，在母系遗传中，较短和较长扩增的增加幅度相似。在三种临床亚型中，伴有肌张力障碍的MJD I型在该基因的CAG重复序列中显示出比其他类型更大程度的扩增以及更年轻的发病年龄。
