SPINOCEREBELLAR ATAXIA TYPE-I AND MACHADO-JOSEPH DISEASE - INCIDENCE OF CAG EXPANSIONS AMONG ADULT-ONSET ATAXIA PATIENTS FROM 311 FAMILIES WITH DOMINANT, RECESSIVE, OR SPORADIC ATAXIA

The ataxias are a complex group of diseases with both environmental an d genetic causes. Among the autosomal dominant forms of ataxia the gen es for two, spinocerebellar ataxia type 1 (SCA1) and Machado-Joseph di sease (MJD), have been isolated. In both of these disorders the molecu lar basis of disease is the expansion of an unstable CAG trinucleotide repeat. To assess the frequency of the SCA1 and MJD trinucleotide rep eat expansions among individuals diagnosed with ataxia we have collect ed DNA from individuals representing 311 families with adult-onset ata xia of unknown etiology and screened these samples for trinucleotide r epeat expansions within the SCA1 and MJD genes. Within this group ther e are 149 families with dominantly inherited ataxia. Of these, 3% had SCA1 trinucleotide repeat expansions, whereas 21% were positive for th e MJD trinucleotide expansion. Thus, together SCA1 and MJD represent 2 4% of the autosomal dominant ataxias in our group, and the frequency o f MJD is substantially greater than that of SCA1. For the 57 patients with MJD trinucleotide repeat expansions, a strong inverse correlation between CAG repeat size and age at onset was observed (r = -.838). Am ong the MJD patients, the normal and affected ranges of CAG repeat siz e are 14-40 and 68-82 repeats, respectively. For SCA1 the normal and a ffected ranges are much closer, containing 19-38 and 40-81 CAG repeats , respectively.