title: Intrafamilial variability of Parkinson phenotype in SCAs: novel cases due to SCA2 and SCA3 expansions.
abstract: BACKGROUND
  Parkinson's disease (PD) has been related to mutations associated with spinocerebellar ataxias (SCA); the frequency of the diagnosis of these mutations is low in general late-onset PD cases. Our aim was to investigate a selected high-risk group of PD patients.
  
  
  METHODS
  PD patients with autosomal dominant inheritance or atypical neurological manifestations were enrolled, underwent a full neurological examination and had the CAG tracts of their SCA1, 2, 3, 6 and 7 genes analyzed.
  
  
  RESULTS
  Of the 23 studied families, two SCA3 and one SCA2 cases were identified. All had autosomal dominant inheritance. In the SCA2 pedigree, four affected sibs had a homogeneous PD phenotype. CAG repeats varied between 35 and 44 with CAA interruptions. Intrafamilial phenotypic heterogeneity was identified in the SCA3 pedigrees; parkinsonian and ataxic phenotypes coexisted in both kindreds. CAGn varied between 69 and 71 repeats. Age of onset was lower in the SCA3 patients than in the remaining 24 cases (38 versus 46.7+/-12 years of age, p=0.003).
  
  
  CONCLUSIONS
  SCA2 and SCA3 mutations were detected in 13% of the present sample: the strategy of selecting a high-risk group increased the rate of making these diagnoses. The SCA2 cases confirmed an association between PD and interrupted expansions, as well as PD intrafamilial phenotypic homogeneity. Clinical heterogeneity of SCA3 pedigrees suggests that disease-modifying agents outside the MJD1 gene may play a role in determining PD symptoms in this disorder.
authors.affiliation: Medical Sciences, Postgraduate Program, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: M P
authors.initials: MP
authors.lastname: Socal
authors.forename: V E
authors.initials: VE
authors.lastname: Emmel
authors.forename: C R M
authors.initials: CR
authors.lastname: Rieder
authors.forename: A
authors.initials: A
authors.lastname: Hilbig
authors.forename: M L
authors.initials: ML
authors.lastname: Saraiva-Pereira
authors.forename: L B
authors.initials: LB
authors.lastname: Jardim
mesh_terms: D000328:Adult; D017668:Age of Onset; D000978:Antiparkinson Agents / Q000627:therapeutic use; D000067699:Ataxin-3; D000067528:Ataxins; D042622:DNA Repeat Expansion; D005190:Family; D005260:Female; D005799:Genes, Dominant; D014644:Genetic Variation; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D017827:Machado-Joseph Disease / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics; D013132:Spinocerebellar Degenerations / Q000235:genetics
chemical_list: D000978:Antiparkinson Agents; D000067528:Ataxins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D007980:Levodopa; C092341:ATXN3 protein, human; D000067699:Ataxin-3