title: Alpha-synuclein gene duplication: marked intrafamilial variability in two novel pedigrees.
abstract: BACKGROUND
  Multiplications of the SNCA gene that encodes alpha-synuclein are a rare cause of autosomal dominant Parkinson's disease (PD).
  
  
  METHODS
  Here, we describe 2 novel families in which there is autosomal dominant PD associated with SNCA duplication, and we compare the clinical features of all known patients carrying 3 or 4 SNCA copies.
  
  
  RESULTS
  Affected members in family A presented with early onset PD that was variably associated with nonmotor features, such as dysautonomia, cognitive deficits, and psychiatric disturbances. In family B, the clinical presentation ranged from early onset PD-dementia with psychiatric disturbances to late onset PD with mild cognitive impairment.
  
  
  CONCLUSIONS
  The presence of 4 SNCA copies is associated with a rich phenotype, characterized by earlier onset of motor and nonmotor features compared with patients who bear 3 SNCA copies. The clinical spectrum associated with SNCA duplications is wide, even within a single family, suggesting a role for as yet unidentified genetic or environmental modifiers.
authors.affiliation: Neurologia I, Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Antonio E
authors.initials: AE
authors.lastname: Elia
authors.forename: Simona
authors.initials: S
authors.lastname: Petrucci
authors.forename: Alfonso
authors.initials: A
authors.lastname: Fasano
authors.forename: Marco
authors.initials: M
authors.lastname: Guidi
authors.forename: Stefano
authors.initials: S
authors.lastname: Valbonesi
authors.forename: Laura
authors.initials: L
authors.lastname: Bernardini
authors.forename: Federica
authors.initials: F
authors.lastname: Consoli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ferraris
authors.forename: Alberto
authors.initials: A
authors.lastname: Albanese
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D020440:Gene Duplication / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000235:genetics*; D010375:Pedigree; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D051844:alpha-Synuclein