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High prevalence of LRRK2 mutations in familial and sporadic Parkinson's disease in Portugal
Author(s) -
Ferreira Joaquim J.,
Guedes Leonor Correia,
Rosa Mário Miguel,
Coelho Miguel,
van Doeselaar Marina,
Schweiger Dorothea,
Di Fonzo Alessio,
Oostra Ben A.,
Sampaio Cristina,
Bonifati Vincenzo
Publication year - 2007
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.21525
Subject(s) - lrrk2 , proband , parkin , penetrance , genetics , mutation , haplotype , disease , biology , parkinson's disease , population , phenotype , medicine , gene , genotype , environmental health
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. © 2007 Movement Disorder Society