title: Autosomal dominant Parkinson's disease: Incidence of mutations in LRRK2, SNCA, VPS35 and GBA genes in Brazil.
abstract: BACKGROUND
  Amongst Parkinson's disease (PD) genetic factors, mutations in LRRK2, SNCA, VPS35 and GBA genes are recognized causes of PD. Nonetheless, few genetic screenings have been conducted in families with a history of PD consistent with autosomal dominant inheritance (ADPD), and their relevance to the etiology of PD has been poorly explored in Latin American populations, such as the Brazilian one, with a high degree of admixture.
  
  
  METHODS
  In order to assess the contribution of specific mutations in LRRK2, SNCA, VPS35 and GBA genes to ADPD in Brazil, we conducted the first molecular evaluation in a cohort of 141 index cases from families with ADPD. Genomic DNA was isolated from peripheral blood or saliva, and the molecular analysis was performed by TaqMan allelic discrimination assays or bidirectional sequencing.
  
  
  RESULTS
  Heterozygous mutations in LRRK2 and GBA genes were identified in 10 (7.0%) probands, and all presented typical signs of classical PD. No mutations were found in SNCA or VPS35 genes.
  
  
  CONCLUSIONS
  Our findings in a representative series of index cases from families with ADPD emphasize the important contribution of LRRK2 G2019S and GBA (L444P and N370S) mutations to parkinsonism in Brazilian families. The absence of mutations in VPS35 and SNCA genes reveals that they are uncommon causes of PD in Brazil, corroborating previous studies that also failed to detect these genetic variants in PD patients from other populations. Recent discoveries of novel causative genes of autosomal dominant forms of PD expand the investigative possibilities and should be targeted on future studies.
authors: Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Gabriella de 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: Débora Cristina T
authors: DC
authors: Valença
authors: Brazil Human Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors: Mário
authors: M
authors: Campos
authors: Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Camilla P
authors: CP
authors: da Silva
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: Movement Disorders Unit, Division of Neurology, Hospital Antônio Pedro, Fluminense Federal University, Brazil.
authors: Marco A
authors: MA
authors: Araujo Leite
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: 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: Neuroscience Core, Hospital Clinics, Federal University of Goiás, Brazil; Integrated Neurosciences Institute, Goiás, Brazil.
authors: Delson José
authors: DJ
authors: da Silva
authors: University Hospital Getúlio Vargas, Federal University of Amazonas, Amazonas, Brazil.
authors: Marcus V
authors: MV
authors: Della Coletta
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: Andressa P
authors: AP
authors: Gonçalves
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
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
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil; D015331:Cohort Studies; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D033921:Vesicular Transport Proteins / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: C497604:SNCA protein, human; C419573:VPS35 protein, human; D033921:Vesicular Transport Proteins; D051844:alpha-Synuclein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: Autosomal dominant Parkinson’s disease; GBA; LRRK2; Parkinson’s disease; SNCA; VPS35