A large Japanese family with Machado-Joseph disease: clinical and genetic analysis

We report clinical and genetic studies on a large Japanese family with Machado-Joseph disease (MJD), in which various different clinical phenotypes were seen in the same family, i.e., cerebellar ataxia type, severe amyotrophy type, and young-onset parkinsonism type. In addition, patients with very mild symptoms (formes frustes) were encountered. The expansion of the CAG repeat at the MJD locus ranged from 64 to 71 in 7 affected and 4 presymptomatic individuals. In our family, no clear inverse correlation was noted between the length of CAG-expansion and the age of onset, or the clinical phenotypes. Hyporeflexia was a common manifestation seen in 5 patients. It has been reported that the presence of peripheral neuropathy in MJD is associated with smaller increase in the CAG repeats; findings in our family conform with this observation.