SPINOCEREBELLAR ATAXIA, TYPE-3 (SCA3) IS GENETICALLY IDENTICAL TO MACHADO-JOSEPH DISEASE (MJD)

Spinocerebellar ataxia, type 3 (SCA3) and Machado-Joseph disease (MJD) are two clinically distinct representatives of the heterogeneous grou p of autosomal dominant cerebellar ataxias. Assignment of the disease genes to the same region of the long arm of chromosome 14 in both SCA3 and MJD suggested that these two disorders are genetically identical. The recent identification of a trinucleotide (GAG) repeat expansion i n a gene underlying MJD facilitates assessment of this hypothesis. We analysed the MJD gene in members of a family with characteristic featu res of SCA3 and no symptoms typical of MJD. We found the same trinucle otide repeat expansion within the gene that was previously described i n patients with MJD. The findings demonstrate that SCA3 and MJD are ge netically identical in spite of their pronounced clinical differences. Furthermore, we demonstrate a striking variation in the copy number o f the CAG repeat among affected members of the same family.