title: Exon dosage variations in Brazilian patients with Parkinson's disease: analysis of SNCA, PARKIN, PINK1 and DJ-1 genes.
abstract: Parkinson's disease is one of the most common neurodegenerative disorders associated with aging, reaching ∼ 2% of individuals over 65 years. Knowledge achieved in the last decade about the genetic basis of Parkinson's disease clearly shows that genetic factors play an important role in the etiology of this disorder. Exon dosage variations account for a high proportion of Parkinson's disease mutations, mainly for PARKIN gene. In the present study, we screened genomic rearrangements in SNCA, PARKIN, PINK1 and DJ-1 genes in 102 Brazilian Parkinson's disease patients with early onset (age of onset ⩽ 50 years), using the multiplex ligation-dependent probe amplification method. Family history was reported by 24 patients, while 78 were sporadic cases. Screening of exon dosage revealed PARKIN and PINK1 copy number variations, but no dosage alteration was found in SNCA and DJ-1 genes. Most of the carriers harbor heterozygous deletions or duplications in the PARKIN gene and only one patient was found to have a deletion in PINK1 exon 1. Data about dosage changes are scarce in the Brazilian population, which stresses the importance of including exon dosage analysis in Parkinson's disease genetic studies.
authors.affiliation: Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Karla Cristina Vasconcelos
authors.initials: KC
authors.lastname: Moura
authors.forename: Mário Campos
authors.initials: MC
authors.lastname: Junior
authors.forename: Ana Lúcia Zuma
authors.initials: AL
authors.lastname: de Rosso
authors.forename: Denise Hack
authors.initials: DH
authors.lastname: Nicaretta
authors.forename: João Santos
authors.initials: JS
authors.lastname: Pereira
authors.forename: Delson
authors.initials: D
authors.lastname: José Silva
authors.forename: Cíntia Barros
authors.initials: CB
authors.lastname: Santos-Rebouças
authors.forename: Márcia Mattos Gonçalves
authors.initials: MM
authors.lastname: Pimentel
mesh_terms: D000328:Adult; D017668:Age of Onset; D001938:Brazil; D016022:Case-Control Studies; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D006579:Heterozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics*; D017384:Sequence Deletion; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase; C497604:SNCA protein, human; C111567:parkin protein; C105131:PARK7 protein, human