title: Mutations in American families with spinocerebellar ataxia (SCA) type 3: SCA3 is allelic to Machado-Joseph disease.
abstract: We identified an expansion of the CAG trinucleotide repeat in the coding region of the Machado-Joseph disease gene in 7 of 24 American families diagnosed with autosomal dominant ataxia. All affected individuals were heterozygous for an expanded allele that ranged from 67 to more than 200 CAG repeats, whereas the normal allele had 14 to 33 repeats. In contrast to the Azorean-Portuguese origins of Machado-Joseph disease, the two largest American families were of German and Dutch-African descent. Clinical, pathologic, and genetic evaluations suggest that American families with spinocerebellar ataxia type 3 differ from those with Machado-Joseph disease by their ethnic origins, predominant spinopontine atrophy, lack of dystonic features, and larger CAG repeat expansion.
authors.affiliation: Clinical Neurogenetics Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892-1430, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Higgins
authors.forename: L E
authors.initials: LE
authors.lastname: Nee
authors.forename: O
authors.initials: O
authors.lastname: Vasconcelos
authors.forename: S E
authors.initials: SE
authors.lastname: Ide
authors.forename: C
authors.initials: C
authors.lastname: Lavedan
authors.forename: L G
authors.initials: LG
authors.lastname: Goldfarb
authors.forename: M H
authors.initials: MH
authors.lastname: Polymeropoulos
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D017827:Machado-Joseph Disease / Q000235:genetics* / Q000503:physiopathology; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid; D013132:Spinocerebellar Degenerations / Q000235:genetics* / Q000503:physiopathology