Author(s):
Brás, José 
; Guerreiro, Rita ; Ribeiro, Maria ; Morgadinho, Ana ; Januario, Cristina ; Dias, Margarida ; Calado, Ana ; Semedo, Cristina ; Oliveira, Catarina ; Hardy, John ; Singleton, Andrew
Date: 2008
Persistent ID: http://hdl.handle.net/10316/11824
Origin: Estudo Geral - Universidade de Coimbra
Description
Background: Mutations in the genes PRKN and LRRK2 are the most frequent known genetic
lesions among Parkinson's disease patients. We have previously reported that in the Portuguese
population the LRRK2 c.6055G > A; p.G2019S mutation has one of the highest frequencies in
Europe.
Methods: Here, we follow up on those results, screening not only LRRK2, but also PRKN, SNCA
and PINK1 in a cohort of early-onset and late-onset familial Portuguese Parkinson disease patients.
This series comprises 66 patients selected from a consecutive series of 132 patients. This selection
was made in order to include only early onset patients (age at onset below 50 years) or late-onset
patients with a positive family history (at least one affected relative). All genes were sequenced bidirectionally,
and, additionally, SNCA, PRKN and PINK1 were subjected to gene dosage analysis.
Results: We found mutations both in LRRK2 and PRKN, while the remaining genes yielded no
mutations. Seven of the studied patients showed pathogenic mutations, in homozygosity or
compound heterozygosity for PRKN, and heterozygosity for LRRK2.
Conclusion: Mutations are common in Portuguese patients with Parkinson's disease, and these
results clearly have implications not only for the genetic diagnosis, but also for the genetic
counseling of these patients.
