Analysis of CAO trinucleotide expansion associated with Machado-Joseph Disease (MJD)

Machado-Joseph disease (MJD)is an autosomal dominant neurodegenerative disorder characterized by cercbellar ataxia, pyramidal and extrapyramidal signs, amyotrophy, peripheral nerve palsy, external ophthalmoplegia and bulging eyes. A recent study has identified an unstable trinucleotide CAG repeat expansion as the mutation causing MJD. Twenty cases of MJD in 13 unrelated Japanese families were genetically and clinically examined in comparison with 20 cases of age at onset- and duration-matched spinocerebellar ataxia type l (SCA1). The CAG repeat number of expanded MJD and SCA1 allele was 72.2 ±3.1 (mean ±SD), and 47.3 ±4.4, respectively. The repeat size was inversely correlated with age at onset, and the repeat number in leukocytes increased from parents to children with acceleration of age at onset (anticipation) in both MJD and SCA1. MJD was clinically characterized by a relatively higher frequency of ocular signs such as eyelid retraction, bulging eyes, ophthalmoparesis, and nystagmus, spasticity in lower limbs, and sensory and urinary disturbances in contrast to the SCA1 patients except for slow eye movement. These results suggest that the expanded CAG repeat and clinical features are correlated in both MJD and SCA1, and MJD can be differentiated from SCA1 by clinical characteristics as well as DNA analysis.