[Clinical and molecular genetic studies of Machado-Joseph disease].

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.