title: Parkinson disease: α-synuclein mutational screening and new clinical insight into the p.E46K mutation.
abstract: BACKGROUND
  Amongst Parkinson's disease-causing genetic factors, missense mutations and genomic multiplications in the gene encoding α-synuclein are well established causes of the disease, although genetic data in populations with a high degree of admixture, such as the Brazilian one, are still scarce.
  
  
  METHODS
  In this study, we conducted a molecular screening of α-synuclein point mutations and copy number variation in the largest cohort of Brazilian patients with Parkinson's disease (n = 549) and also in twelve Portuguese and one Bolivian immigrants. Genomic DNA was isolated from peripheral blood leukocytes or saliva, and the mutational screening was performed by quantitative and qualitative real-time PCR.
  
  
  RESULTS
  The only alteration identified was the p.E46K mutation in a 60-year-old man, born in Bolivia, with a familial history of autosomal dominant Parkinson's disease. This is the second family ever reported, in which this rare pathogenic mutation is segregating. The same mutation was firstly described ten years ago in a Spanish family with a neurodegenerative syndrome combining parkinsonism, dementia and visual hallucinations. The clinical condition of our proband reveals a less aggressive phenotype than previously described and reinforces that marked phenotypic heterogeneity is common among patients with Parkinson's disease, even among those carriers sharing the same mutation.
  
  
  CONCLUSIONS
  Our findings add new insight into the preexisting information about α-synuclein p.E46K, improving our understanding about the endophenotypes associated to this mutation and corroborate that missense alterations and multiplications in α-synuclein are uncommon among Brazilian patients with Parkinson's disease.
authors: Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: pimentel@uerj.br.
authors: Márcia M G
authors: MM
authors: Pimentel
authors: Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Fabíola C
authors: FC
authors: Rodrigues
authors: Movement Disorders Unit, Division of Neurology, University Hospital Antônio Pedro, Fluminense Federal University, Brazil.
authors: Marco Antônio A
authors: MA
authors: Leite
authors: Brazil Human Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors: Mário
authors: M
authors: Campos Júnior
authors: University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Ana Lucia
authors: AL
authors: Rosso
authors: Santa Casa da Misericórdia do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Denise H
authors: DH
authors: Nicaretta
authors: Movement Disorders Section, Neurology Service, Pedro Ernesto University Hospital, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: João S
authors: JS
authors: Pereira
authors: Neuroscience Core, Hospital Clinics, Federal University of Goiás, Brazil; Integrated Neurosciences Institute, Goiás, Brazil.
authors: Delson José
authors: DJ
authors: Silva
authors: University Hospital Getúlio Vargas, Federal University of Amazonas, Amazonas, Brazil.
authors: Marcus V
authors: MV
authors: Della Coletta
authors: Institute of Neurology Deolindo Couto, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Federal Hospital of Servidores do Estado, Rio de Janeiro, Brazil.
authors: Luiz Felipe R
authors: LF
authors: Vasconcellos
authors: Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Gabriella M
authors: GM
authors: Abreu
authors: Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Jussara M
authors: JM
authors: Dos Santos
authors: Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Cíntia B
authors: CB
authors: Santos-Rebouças
mesh_terms: D000368:Aged; D001938:Brazil; D005190:Family; D005260:Female; D014644:Genetic Variation; D015894:Genome, Human; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D017354:Point Mutation; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D051844:alpha-Synuclein
keywords: Copy number variation; Parkinson's disease; SNCA; p.E46K mutation; α-synuclein