title: High prevalence of LRRK2 mutations in familial and sporadic Parkinson's disease in Portugal.
abstract: Mutations in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene are the most frequent known cause of Parkinson's disease (PD), but their prevalence varies markedly between populations. Here we studied the frequency and associated phenotype of four recurrent LRRK2 mutations (R1441C, R1441G, R1441H, and G2019S) in familial and sporadic PD from a single referral center in Lisbon, Portugal. Among 138 unrelated PD probands, we identified 9 heterozygous G2019S carriers (6.52%) and 1 heterozygous R1441H carrier (0.72%). The G2019S mutation was present in 4 of the 107 sporadic (3.74%) and in 5 of the 31 familial probands (16.1%). Mutations were not found among 101 Portuguese controls. The G2019S mutation was present on a single haplotype and displayed reduced penetrance. Heterozygous parkin gene mutations were also found in 2 G2019S-positive probands, but their pathogenic role is unclear. The clinical phenotype in patients with LRRK2 mutations was indistinguishable from that of typical PD, including impaired sense of smell. The G2019S mutation is a very common genetic determinant among the Portuguese patients with PD, and the R1441H mutation is also present in this population. These data have important implications for the diagnostic work-up and genetic counseling of patients with this disease in Portugal.
authors.affiliation: Neurological Clinic Research Unit, Institute of Molecular Medicine, Lisbon School of Medicine, Lisbon, Portugal. v.bonifati@erasmusmc.nl
authors.forename: Joaquim J
authors.initials: JJ
authors.lastname: Ferreira
authors.forename: Leonor Correia
authors.initials: LC
authors.lastname: Guedes
authors.forename: Mário Miguel
authors.initials: MM
authors.lastname: Rosa
authors.forename: Miguel
authors.initials: M
authors.lastname: Coelho
authors.forename: Marina
authors.initials: M
authors.lastname: van Doeselaar
authors.forename: Dorothea
authors.initials: D
authors.lastname: Schweiger
authors.forename: Alessio
authors.initials: A
authors.lastname: Di Fonzo
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Cristina
authors.initials: C
authors.lastname: Sampaio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bonifati
mesh_terms: D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D011174:Portugal / Q000453:epidemiology; D015995:Prevalence; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases