LRRK2 G2019S and R1441G mutations associated with Parkinson’s disease are common in the Basque Country, but relative prevalence is determined by ethnicity
Mutations in LRRK2 gene are the most frequent cause of Parkinson’s disease (PD) described, but their prevalence varies between populations. Patients, 418, with PD and 138 unrelated controls from the Basque Country were screened for LRRK2 G2019S and R1441G mutations. Of the patients, 3.82% were heterozygous carriers of G2019S and 13.15% of R1441G. G2019S frequency was higher in non-Basque population (6.0%), while R1441G was more common in Basque origin population (22.4%). Our conclusion is that both G2019S and R1441G mutations’ frequency varies markedly between Basque and non-Basque origin population reinforcing the importance of ethnicity consideration when establishing mutation prevalence.
KeywordsLRRK2 Mutation frequency Population heterogeneity Late-onset Parkinson’s disease
- 1.Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, Lopez de Munain A, Aparicio S, Gil AM, Khan N, Johnson J, Martinez JR, Nicholl D, Carrera IM, Pena AS, de Silva R, Lees A, Marti-Masso JF, Perez-Tur J, Wood NW, Singleton AB (2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson’ disease. Neuron 44:595–600. doi:10.1016/j.neuron.2004.10.023 CrossRefPubMedGoogle Scholar
- 2.Di Fonzo A, Rohe CF, Ferreira J, Chien HF, Vacca L, Stocchi F, Guedes L, Fabrizio E, Manfredi M, Vanacore N, Goldwurm S, Breedveld G, Sampaio C, Meco G, Barbosa E, Oostra BA, Bonifati V (2005) A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease. Lancet 365:412–415PubMedGoogle Scholar
- 6.Simon-Sanchez J, Marti-Masso JF, Sanchez-Mut JV, Paisan-Ruiz C, Martinez-Gil A, Ruiz-Martinez J, Saenz A, Singleton AB, Lopez de Munain A, Perez-Tur J (2006) Parkinson’s disease due to the R1441G mutation in Dardarin: a founder effect in the Basques. Mov Disord 21:1954–1959. doi:10.1002/mds.21114 CrossRefPubMedGoogle Scholar
- 7.Healy DG, Falchi M, O’Sullivan SS, Bonifati V, Durr A, Bressman S, Brice A, Aasly J, Zabetian CP, Goldwurm S, Ferreira JJ, Tolosa E, Kay DM, Klein C, Williams DR, Marras C, Lang AE, Wszolek ZK, Berciano J, Schapira AH, Lynch T, Bhatia KP, Gasser T, Lees AJ, Wood NW (2008) Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson’ disease: a case-control study. Lancet Neurol 7:583–590. doi:10.1016/S1474-4422(08)70117-0 CrossRefPubMedGoogle Scholar
- 11.Gonzalez-Fernandez MC, Lezcano E, Ross OA, Gomez-Esteban JC, Gomez-Busto F, Velasco F, Alvarez-Alvarez M, Rodriguez-Martinez MB, Ciordia R, Zarranz JJ, Farrer MJ, Mata IF, de Pancorbo MM (2007) Lrrk2-associated parkinsonism is a major cause of disease in Northern Spain. Parkinsonism Relat Disord 13:509–515. doi:10.1016/j.parkreldis.2007.04.003 CrossRefPubMedGoogle Scholar