Affiliations: Instituto de Biologia Roberto Alcantara Gomes,
Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil | Hospital Universitário Clementino Fraga Filho,
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil | Universidade Gama Filho, Rio de Janeiro, Brazil | Faculdade de Ciências Médicas, Centro
Biomédico, Universidade do Estado do Rio de Janeiro, Rio de Janeiro,
Brazil | Núcleo Neurociências, Hospital das
Clínicas, Universidade Federal de Goiás, Goiás, Brazil | Instituto Integrado de Neurociências, Goiás,
Brazil
Note: [] Corresponding author: Departamento de Genética, Instituto de
Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rua
São Francisco Xavier, 524, PHLC, sala 501F. Rio de Janeiro, Brazil. Tel.:
+55 21 2334-0039; E-mail: pimentel@uerj.br
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.
Keywords: Copy number variation, early-onset, MLPA, Deletion, Duplication
