Neurogenetics

, Volume 6, Issue 4, pp 171–177

Lrrk2 pathogenic substitutions in Parkinson's disease

  • Ignacio F. Mata
  • Jennifer M. Kachergus
  • Julie P. Taylor
  • Sarah Lincoln
  • Jan Aasly
  • Timothy Lynch
  • Mary M. Hulihan
  • Stephanie A. Cobb
  • Ruey-Meei Wu
  • Chin-Song Lu
  • Carlos Lahoz
  • Zbigniew K. Wszolek
  • Matthew J. Farrer
Original Article

DOI: 10.1007/s10048-005-0005-1

Cite this article as:
Mata, I.F., Kachergus, J.M., Taylor, J.P. et al. Neurogenetics (2005) 6: 171. doi:10.1007/s10048-005-0005-1

Abstract

Leucine-rich repeat kinase 2 (LRRK2) mutations have been implicated in autosomal dominant parkinsonism, consistent with typical levodopa-responsive Parkinson's disease. The gene maps to chromosome 12q12 and encodes a large, multifunctional protein. To identify novel LRRK2 mutations, we have sequenced 100 affected probands with family history of parkinsonism. Semiquantitative analysis was also performed in all probands to identify LRRK2 genomic multiplication or deletion. In these kindreds, referred from movement disorder clinics in many parts of Europe, Asia, and North America, parkinsonism segregates as an autosomal dominant trait. All 51 exons of the LRRK2 gene were analyzed and the frequency of all novel sequence variants was assessed within controls. The segregation of mutations with disease has been examined in larger, multiplex families. Our study identified 26 coding variants, including 15 nonsynonymous amino acid substitutions of which three affect the same codon (R1441C, R1441G, and R1441H). Seven of these coding changes seem to be pathogenic, as they segregate with disease and were not identified within controls. No multiplications or deletions were identified.

Keywords

LRRK2KinaseIdiopathic Parkinson's diseaseMutationPolymorphism

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Ignacio F. Mata
    • 1
  • Jennifer M. Kachergus
    • 1
  • Julie P. Taylor
    • 1
  • Sarah Lincoln
    • 1
  • Jan Aasly
    • 2
  • Timothy Lynch
    • 3
    • 4
  • Mary M. Hulihan
    • 1
  • Stephanie A. Cobb
    • 1
  • Ruey-Meei Wu
    • 5
  • Chin-Song Lu
    • 6
  • Carlos Lahoz
    • 7
  • Zbigniew K. Wszolek
    • 1
  • Matthew J. Farrer
    • 1
    • 8
  1. 1.Departments of Neurology and NeuroscienceMayo ClinicJacksonvilleUSA
  2. 2.Department of NeurologySt. Olav's HospitalTrondheimNorway
  3. 3.Department of NeurologyMater Misericordiae University HospitalDublinIreland
  4. 4.Conway Institute of Biomolecular and Biomedical ResearchDublinIreland
  5. 5.Department of Neurology, National Taiwan University Hospital, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  6. 6.Department of NeurologyChang Gung Memorial HospitalTaoyuanTaiwan
  7. 7.Servicio de NeurologíaHospital Universitario Central de AsturiasOviedoSpain
  8. 8.Department of NeuroscienceMolecular Genetics Laboratory and Core, Morris K. Udall Parkinson's Disease Research Center of ExcellenceJacksonvilleUSA