[Molecular genetics of Machado-Joseph disease]

Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration. The CAG expansions of the MJD1 gene at chromosome 14q32.1 was identified as the cause of the disease. MJD has three factors that influence the age of the onset. The MJD1 repeat length inversely correlated with the age of onset (r = -0.87). Homozygosity of the gene exhibited an additive effect on age of onset. MJD has a gender-specific effect on the age of onset. A parent-child analysis showed the unidirectional expansion of CAG repeats. 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.