neurogenetics

, 10:157 | Cite as

LRRK2 G2019S and R1441G mutations associated with Parkinson’s disease are common in the Basque Country, but relative prevalence is determined by ethnicity

  • A. Gorostidi
  • J. Ruiz-Martínez
  • A. Lopez de Munain
  • A. Alzualde
  • J. F. Martí Massó
Short Communication

Abstract

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.

Keywords

LRRK2 Mutation frequency Population heterogeneity Late-onset Parkinson’s disease 

Supplementary material

10048_2008_162_MOESM1_ESM.ppt (44 kb)
Supplemental Figure 1Reported frequencies of LRRK2 G2019S and R1441G mutations in different regions of the Iberian Peninsula according to literature and our study [4, 7, 9, 10, 11]. Frequencies are expressed as number of mutation carrier patients per total PD analyzed patients for each study (PPT 44.0 KB)

References

  1. 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. 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
  3. 3.
    Lesage S, Ibanez P, Lohmann E, Pollak P, Tison F, Tazir M, Leutenegger AL, Guimaraes J, Bonnet AM, Agid Y, Durr A, Brice A (2005) G2019S LRRK2 mutation in French and North African families with Parkinson's disease. Ann Neurol 58:784–787. doi:10.1002/ana.20636 CrossRefPubMedGoogle Scholar
  4. 4.
    Ferreira JJ, Guedes LC, Rosa MM, Coelho M, van Doeselaar M, Schweiger D, Di Fonzo A, Oostra BA, Sampaio C, Bonifati V (2007) High prevalence of LRRK2 mutations in familial and sporadic Parkinson's disease in Portugal. Mov Disord 22:1194–1201. doi:10.1002/mds.21525 CrossRefPubMedGoogle Scholar
  5. 5.
    Papapetropoulos S, Adi N, Shehadeh L, Bishopric N, Singer C, Argyriou AA, Chroni E (2008) Is the G2019S LRRK2 mutation common in all southern European populations? J Clin Neurosci 15:1027–1030CrossRefPubMedGoogle Scholar
  6. 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. 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
  8. 8.
    Gelb DJ, Oliver E, Gilman S (1999) Diagnostic criteria for Parkinson disease. Arch Neurol 56:33–39. doi:10.1001/archneur.56.1.33 CrossRefPubMedGoogle Scholar
  9. 9.
    Mata IF, Ross OA, Kachergus J, Huerta C, Ribacoba R, Moris G, Blazquez M, Guisasola LM, Salvador C, Martinez C, Farrer M, Alvarez V (2006) LRRK2 mutations are a common cause of Parkinson’ disease in Spain. Eur J Neurol 13:391–394. doi:10.1111/j.1468-1331.2006.01256.x CrossRefPubMedGoogle Scholar
  10. 10.
    Gaig C, Ezquerra M, Marti MJ, Munoz E, Valldeoriola F, Tolosa E (2006) LRRK2 mutations in Spanish patients with Parkinson disease: frequency, clinical features, and incomplete penetrance. Arch Neurol 63:377–382. doi:10.1001/archneur.63.3.377 CrossRefPubMedGoogle Scholar
  11. 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

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • A. Gorostidi
    • 2
    • 3
  • J. Ruiz-Martínez
    • 1
    • 3
  • A. Lopez de Munain
    • 1
  • A. Alzualde
    • 2
    • 3
  • J. F. Martí Massó
    • 1
  1. 1.Department of NeurologyHospital DonostiaDonostia - San SebastiánSpain
  2. 2.Neurogenetics LaboratoryHospital DonostiaDonostia-San SebastiánSpain
  3. 3.CIBERNEDMadridSpain

Personalised recommendations