title: Machado-Joseph disease in three Scandinavian families.
abstract: Machado-Joseph disease (MJD) is an autosomal dominantly inherited neurodegenerative disorder characterized by varying age of onset and pronounced phenotypic heterogeneity. The clinical core features include gait ataxia, external ophthalmoplegia, nystagmus, and bulging eyes. Recently, Kawagushi et al. (1994) cloned the MJD1 gene on chromosome 14 and MJD turned out to be the fifth neurodegenerative disease caused by an unstable CAG repeat expansion. We have studied two large Danish families and one Norwegian family with MJD. Three features not previously associated with MJD are reported: dementia, generalized muscle and joint pain, and in one case neuropathological examination revealed atrophy of the inferior olives. We found a significant inverse correlation between age of onset and the length of the CAG repeat expansion, and anticipation is described through four succeeding generations. Instability of the CAG repeat expansion was most pronounced at paternal transmission.
authors.affiliation: Institute of Medical Biochemistry and Genetics, The Panum Institute, University of Copenhagen, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Løkkegaard
authors.forename: J E
authors.initials: JE
authors.lastname: Nielsen
authors.forename: L
authors.initials: L
authors.lastname: Hasholt
authors.forename: K
authors.initials: K
authors.lastname: Fenger
authors.forename: L
authors.initials: L
authors.lastname: Werdelin
authors.forename: L
authors.initials: L
authors.lastname: Tranebjaerg
authors.forename: M
authors.initials: M
authors.lastname: Lauritzen
authors.forename: E
authors.initials: E
authors.lastname: Colding-Jørgensen
authors.forename: M
authors.initials: M
authors.lastname: Grønbech-Jensen
authors.forename: O A
authors.initials: OA
authors.lastname: Henriksen
authors.forename: S A
authors.initials: SA
authors.lastname: Sørensen
mesh_terms: D000328:Adult; D000368:Aged; D000067699:Ataxin-3; D003704:Dementia / Q000235:genetics; D005260:Female; D006801:Humans; D017827:Machado-Joseph Disease / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins; D010375:Pedigree; D010641:Phenotype; D012097:Repressor Proteins; D012537:Scandinavian and Nordic Countries; D018911:Trinucleotide Repeats
chemical_list: D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3