The shortest expanded allele of the MJD1 gene in a Chinese MJD kindred with autonomic dysfunction

Machado-Joseph disease (MJD) is the most common type of autosomal dominant spinocerebellar ataxia caused by an expanded CAG repeat in the MJD1 gene. Intermediate CAG alleles have been previously described, and they tend to be associated with unusual manifestations of the nervous system. Here we describe a Chinese kindred with hereditary spinocerebellar ataxia, in which the proband presented with autonomic dysfunction besides the typical features of MJD. DNA analysis confirmed the clinical diagnosis and revealed that the expanded CAG repeat number of the proband is 51, which is the shortest known causative expanded allele. These findings indicate that the clinical entity of MJD can occur with 51 trinucleotide repeats, and that the clinical features of MJD might cover a wider spectrum than previously believed. The high clinical pleomorphism and the phenomenon with the 51-CAG-repeat units caused the disease phenotype in our patient, but the normal phenotype in the individuals from another MJD family strongly supports that the MJD phenotype is modulated by modifier factors.