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BioMed Research International
Volume 2015 (2015), Article ID 678701, 6 pages
http://dx.doi.org/10.1155/2015/678701
Research Article

Evaluating LRRK2 Genetic Variants with Unclear Pathogenicity

Department of Neurology, National Neuroscience Institute, 7 Hospital Drive, Outram Road, Singapore 169611

Received 20 September 2014; Revised 19 January 2015; Accepted 26 January 2015

Academic Editor: Hiroyuki Tomiyama

Copyright © 2015 Fathima Shaffra Refai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. E.-K. Tan and L. M. Skipper, “Pathogenic mutations in Parkinson disease,” Human Mutation, vol. 28, no. 7, pp. 641–653, 2007. View at Publisher · View at Google Scholar · View at Scopus
  2. A. di Fonzo, C. F. Rohé, J. Ferreira et al., “A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease,” The Lancet, vol. 365, no. 9457, pp. 412–415, 2005. View at Publisher · View at Google Scholar · View at Scopus
  3. W. P. Gilks, P. M. Abou-Sleiman, S. Gandhi et al., “A common LRRK2 mutation in idiopathic Parkinson's disease,” The Lancet, vol. 365, no. 9457, pp. 415–416, 2005. View at Publisher · View at Google Scholar · View at Scopus
  4. T. Peeraully and E. K. Tan, “Genetic variants in sporadic parkinson's disease: east vs west,” Parkinsonism and Related Disorders, vol. 18, no. 1, pp. S63–S65, 2012. View at Google Scholar · View at Scopus
  5. J. N. Foo, L. C. Tan, H. Liany et al., “Analysis of non-synonymous-coding variants of Parkinson's disease-related pathogenic and susceptibility genes in East Asian populations,” Human Molecular Genetics, vol. 23, no. 14, pp. 3891–3897, 2014. View at Publisher · View at Google Scholar
  6. E.-K. Tan, R. Peng, Y.-Y. Teo et al., “Multiple LRRK2 variants modulate risk of Parkinson disease: a Chinese multicenter study,” Human Mutation, vol. 31, no. 5, pp. 561–568, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. U. Kumari and E. K. Tan, “LRRK2 in Parkinson's disease: genetic and clinical studies from patients,” FEBS Journal, vol. 276, no. 22, pp. 6455–6463, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. B. Patra, A. J. Parsian, B. A. Racette, J. H. Zhao, J. S. Perlmutter, and A. Parsian, “LRRK2 gene G2019S mutation and SNPs [haplotypes] in subtypes of Parkinson's disease,” Parkinsonism and Related Disorders, vol. 15, no. 3, pp. 175–180, 2009. View at Publisher · View at Google Scholar · View at Scopus
  9. A. Zimprich, S. Biskup, P. Leitner et al., “Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology,” Neuron, vol. 44, no. 4, pp. 601–607, 2004. View at Publisher · View at Google Scholar · View at Scopus
  10. L. Bosgraaf and P. J. M. van Haastert, “Roc, a Ras/GTPase domain in complex proteins,” Biochimica et Biophysica Acta, vol. 1643, no. 1–3, pp. 5–10, 2003. View at Publisher · View at Google Scholar · View at Scopus
  11. R. M. Sancho, B. M. H. Law, and K. Harvey, “Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways,” Human Molecular Genetics, vol. 18, no. 20, pp. 3955–3968, 2009. View at Publisher · View at Google Scholar · View at Scopus
  12. A. B. Singleton, M. J. Farrer, and V. Bonifati, “The genetics of Parkinson's disease: progress and therapeutic implications,” Movement Disorders, vol. 28, no. 1, pp. 14–23, 2013. View at Publisher · View at Google Scholar · View at Scopus
  13. A. S. Chen-Plotkin, W. Yuan, C. Anderson et al., “Corticobasal syndrome and primary progressive aphasia as manifestations of LRRK2 gene mutations,” Neurology, vol. 70, no. 7, pp. 521–527, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. J. P. Covy, W. Yuan, E. A. Waxman, H. I. Hurtig, V. M. van Deerlin, and B. I. Giasson, “Clinical and pathological characteristics of patients with leucine-rich repeat kinase-2 mutations,” Movement Disorders, vol. 24, no. 1, pp. 32–39, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. O. A. Ross, A. I. Soto-Ortolaza, M. G. Heckman et al., “Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study,” The Lancet Neurology, vol. 10, no. 10, pp. 898–908, 2011. View at Publisher · View at Google Scholar · View at Scopus
  16. S. Lesage, C. Condroyer, A. Lannuzel et al., “Molecular analyses of the LRRK2 gene in Europeanand North African autosomal dominant Parkinson's disease,” Journal of Medical Genetics, vol. 46, no. 7, pp. 458–464, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. C. B. Abdalla-Carvalho, C. B. Santos-Rebouças, B. C. Guimarães et al., “Genetic analysis of LRRK2 functional domains in Brazilian patients with Parkinson's disease,” European Journal of Neurology, vol. 17, no. 12, pp. 1479–1481, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. B. Jasinska-Myga, J. Kachergus, C. Vilariño-Güell et al., “Comprehensive sequencing of the LRRK2 gene in patients with familial Parkinson's disease from North Africa,” Movement Disorders, vol. 25, no. 13, pp. 2052–2058, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. K. Nuytemans, R. Rademakers, J. Theuns et al., “Founder mutation p.R1441C in the leucine-rich repeat kinase 2 gene in Belgian Parkinson's disease patients,” European Journal of Human Genetics, vol. 16, no. 4, pp. 471–479, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. L. J. Ozelius, G. Senthil, R. Saunders-Pullman et al., “LRRK2 G2019S as a cause of Parkinson's disease in Ashkenazi Jews,” The New England Journal of Medicine, vol. 354, no. 4, pp. 424–425, 2006. View at Publisher · View at Google Scholar · View at Scopus
  21. D. G. Healy, M. Falchi, S. S. O'Sullivan et al., “Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study,” The Lancet Neurology, vol. 7, no. 7, pp. 583–590, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. W. W. Smith, Z. Pei, H. Jiang, V. L. Dawson, T. M. Dawson, and C. A. Ross, “Kinase activity of mutant LRRK2 mediates neuronal toxicity,” Nature Neuroscience, vol. 9, no. 10, pp. 1231–1233, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. E. Greggio, S. Jain, A. Kingsbury et al., “Kinase activity is required for the toxic effects of mutant LRRK2/dardarin,” Neurobiology of Disease, vol. 23, no. 2, pp. 329–341, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. D. C. Angeles, B.-H. Gan, L. Onstead et al., “Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death,” Human Mutation, vol. 32, no. 12, pp. 1390–1397, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. S. L. Chan, L.-L. Chua, D. C. Angeles, and E.-K. Tan, “MAP1B rescues LRRK2 mutant-mediated cytotoxicity,” Molecular Brain, vol. 7, no. 1, article 29, 2014. View at Publisher · View at Google Scholar · View at Scopus
  26. J. Deng, P. A. Lewis, E. Greggio, E. Sluch, A. Beilina, and M. R. Cookson, “Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 5, pp. 1499–1504, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. B. K. Gilsbach and A. Kortholt, “Structural biology of the LRRK2 GTPase and kinase domains: implications for regulation,” Frontiers in Molecular Neuroscience, vol. 7, article 32, 2014. View at Publisher · View at Google Scholar · View at Scopus
  28. N. D. Jorgensen, Y. Peng, C. C.-Y. Ho et al., “The WD40 domain is required for LRRK2 neurotoxicity,” PLoS ONE, vol. 4, no. 12, Article ID e8463, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. P. P. Pungaliya, Y. Bai, K. Lipinski et al., “Identification and characterization of a leucine-rich repeat kinase 2 (LRRK2) consensus phosphorylation motif,” PLoS ONE, vol. 5, no. 10, Article ID e13672, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. S. Kamikawaji, G. Ito, and T. Iwatsubo, “Identification of the autophosphorylation sites of LRRK2,” Biochemistry, vol. 48, no. 46, pp. 10963–10975, 2009. View at Publisher · View at Google Scholar · View at Scopus