Machado-Joseph disease in four Chinese pedigrees: molecular analysis of 15 patients including two juvenile cases and clinical correlations.

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder associated with the expansion of a (CAG)n array in the MJD1 gene. We analyzed the sizes of the (CAG)n array using DNA samples from 61 members of four Chinese MJD families and 18 Chinese normal control subjects and confirmed that the (CAG)n array in 15 MJD chromosomes was expanded to 72-86 repeat units. There were no subjects with (CAG)n array sizes intermediate between those of normal and MJD affected groups. Meanwhile, we found a significant negative correlation between the age of onset of symptoms and (CAG)n array size. The largest (CAG)n array of 86 repeat units was in the youngest patient, whose age of onset was 5 years. The intergenerational increase in number of CAG repeat units was associated with the clinical phenomenon of anticipation.