title: Analysis of Parkinson disease patients from Portugal for mutations in SNCA, PRKN, PINK1 and LRRK2.
abstract: 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 bi-directionally, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Neurosciences and Cell Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. brasj@nia.nih.gov
authors.forename: Jose
authors.initials: J
authors.lastname: Bras
authors.forename: Rita
authors.initials: R
authors.lastname: Guerreiro
authors.forename: Maria
authors.initials: M
authors.lastname: Ribeiro
authors.forename: Ana
authors.initials: A
authors.lastname: Morgadinho
authors.forename: Cristina
authors.initials: C
authors.lastname: Januario
authors.forename: Margarida
authors.initials: M
authors.lastname: Dias
authors.forename: Ana
authors.initials: A
authors.lastname: Calado
authors.forename: Cristina
authors.initials: C
authors.lastname: Semedo
authors.forename: Catarina
authors.initials: C
authors.lastname: Oliveira
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
mesh_terms: D000368:Aged; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D011174:Portugal / Q000453:epidemiology / Q000208:ethnology; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013912:Threonine / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008715:Methionine; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D013912:Threonine; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase; C497604:SNCA protein, human; C111567:parkin protein; C495280:LRRK2 protein, human