title: Machado Joseph disease is not an allele of the spinocerebellar ataxia 2 locus.
abstract: Machado Joseph disease (MJD) is a progressive, spinocerebellar ataxia (SCA) with an autosomal dominant mode of inheritance and almost complete penetrance. Clinically, it is difficult to distinguish it from other autosomal dominantly inherited ataxias, and it has been suggested that MJD may be caused by an allelic variant of SCA. Exclusion of MJD from the SCA1 locus on chromosome 6p has previously been demonstrated. However, following the recent assignment of a second locus for spinocerebellar ataxia (SCA2) to chromosome 12q in a large Cuban kindred of Spanish origin, we have investigated linkage in MJD families using the two markers, D12S58 and PLA2, that flank this disease gene. The MJD locus was definitively excluded from an interval spanning approximately 70 cM, which includes these loci. These studies demonstrate that MJD and SCA2 are genetically distinct despite similarities in disease phenotype and ancestral origins of the patients. Thus, the as yet unmapped MJD locus represents a third SCA locus, providing further evidence for genetic heterogeneity within these disorders.
authors.affiliation: Centre for Research in Neuroscience, McGill University, Montreal, Canada.
authors.forename: E C
authors.initials: EC
authors.lastname: Twist
authors.forename: L A
authors.initials: LA
authors.lastname: Farrer
authors.forename: P M
authors.initials: PM
authors.lastname: Macleod
authors.forename: J
authors.initials: J
authors.lastname: Radvany
authors.forename: S
authors.initials: S
authors.lastname: Chamberlain
authors.forename: R N
authors.initials: RN
authors.lastname: Rosenberg
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D000483:Alleles; D002460:Cell Line; D002881:Chromosomes, Human, Pair 12; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D017827:Machado-Joseph Disease / Q000235:genetics*; D008297:Male; D010375:Pedigree; D016133:Polymerase Chain Reaction; D013132:Spinocerebellar Degenerations / Q000235:genetics*
chemical_list: D005819:Genetic Markers