title: Early-onset parkinsonism caused by alpha-synuclein gene triplication: Clinical and genetic findings in a novel family.
abstract: BACKGROUND
  Triplications of SNCA, the gene encoding for α-synuclein, cause a very rare Mendelian form of early-onset parkinsonism combined with cognitive and autonomic dysfunctions. Only six families with SNCA triplications have been described so far, limiting our knowledge of the associated phenotype. In this study, we report clinical and genetic findings in a new Italian family with SNCA triplication.
  
  
  METHODS
  The patients' phenotype was assessed by neurological examination, neuropsychological tests, and brain imaging (MRI and SPECT-DaTSCAN). For the genetic investigation, we used three independent techniques: genome-wide SNP microarrays, fluorescence in situ hybridization (FISH), and multiplex ligation-dependent probe amplification (MLPA).
  
  
  RESULTS
  Genetic studies documented the presence of four copies of the SNCA gene in the affected family members. FISH experiments and the segregation in the family were consistent with a heterozygous triplication of the SNCA locus. The patients carrying the SNCA triplication developed early-onset parkinsonism combined with depression, behavior disturbances, sleep disorders, and cognitive decline; marked autonomic dysfunctions were not observed. Brain imaging revealed fronto-parietal atrophy and a severe striatal dopaminergic deficit.
  
  
  CONCLUSIONS
  The identification of this novel family contributes to the genetic and clinical characterization of this rare form. Our data reinforce the view that SNCA triplications cause early-onset parkinsonism, with prominent non-motor features.
authors.affiliation: Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Simone
authors.initials: S
authors.lastname: Olgiati
authors.affiliation: Department of Neuroscience, Imaging, and Medical Sciences, G. d'Annunzio University, Chieti/Pescara, Italy; Aging Research Centre, Ce.S.I., G. d'Annunzio University Foundation, Chieti, Italy.
authors.forename: Astrid
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Quadri
authors.affiliation: Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Guido J
authors.initials: GJ
authors.lastname: Breedveld
authors.affiliation: Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Josja
authors.initials: J
authors.lastname: Graafland
authors.affiliation: Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Eussen
authors.affiliation: Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Hannie
authors.initials: H
authors.lastname: Douben
authors.affiliation: Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Annelies
authors.initials: A
authors.lastname: de Klein
authors.affiliation: Department of Neuroscience, Imaging, and Medical Sciences, G. d'Annunzio University, Chieti/Pescara, Italy; Aging Research Centre, Ce.S.I., G. d'Annunzio University Foundation, Chieti, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Onofrj
authors.affiliation: Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands. Electronic address: v.bonifati@erasmusmc.nl.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bonifati
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D009154:Mutation; D010300:Parkinson Disease / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D035781:Siblings; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: C497604:SNCA protein, human; D051844:alpha-Synuclein
keywords: Gene; Mutation; Parkinsonism; SNCA; Triplication; α-synuclein