The genetic basis of Parkinson's disease
https://doi.org/10.14412/2074-2711-2017-1-96-100
Abstract
Parkinson's disease (PD) is a multifactorial disease that develops in the presence of both genetic and environmental factors. In recent years, there has been sufficient information on the role of genetic predisposition in the development of not only familial cases, but also sporadic ones. A hereditary burden in PD may not be traced in cases of recessive inheritance with a low gene penetrance, as well as in a patient's death before the onset of the disease. Active introduction of molecular genetic methods, including next generation sequencing, can annually identify new gene mutations that underlie sporadic PD cases. This paper provides an overview of the current literature on the genetic aspects of PD with emphasis on the ethnic characteristics of the disease.
About the Authors
A. A. Tappakhov
M.K. Ammosov North-Eastern Federal University
Russian Federation
58, Belinsky St., Yakutsk, 677000
Russian Federation
58, Belinsky St., Yakutsk, 677000
T. E. Popova
M.K. Ammosov North-Eastern Federal University
Russian Federation
58, Belinsky St., Yakutsk, 677000
Russian Federation
58, Belinsky St., Yakutsk, 677000
T. Ya. Nikolaeva
M.K. Ammosov North-Eastern Federal University
Russian Federation
58, Belinsky St., Yakutsk, 677000
Russian Federation
58, Belinsky St., Yakutsk, 677000
P. I. Gurieva
M.K. Ammosov North-Eastern Federal University
Russian Federation
58, Belinsky St., Yakutsk, 677000
Russian Federation
58, Belinsky St., Yakutsk, 677000
N. A. Shnaider
Prof. V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of Russia
Russian Federation
1, Partisan Zheleznyak St., Krasnoyarsk 660022
Russian Federation
1, Partisan Zheleznyak St., Krasnoyarsk 660022
M. M. Petrova
Prof. V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of Russia
Russian Federation
1, Partisan Zheleznyak St., Krasnoyarsk 660022
Russian Federation
1, Partisan Zheleznyak St., Krasnoyarsk 660022
M. R. Sapronova
Prof. V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of Russia
Russian Federation
1, Partisan Zheleznyak St., Krasnoyarsk 660022
Russian Federation
1, Partisan Zheleznyak St., Krasnoyarsk 660022
References
1. Левин ОС, Федорова НВ. Болезнь Паркинсона. Москва: МЕДПресс-информ; 2012. 352 c. [Levin OS, Fedorova NV. Bolezn' Parkinsona [Parkinson’s disease]. Moscow: MEDPress- inform; 2012. 352 p.]
2. Heumann R, Moratalla R, Herrero MT, et al. Dyskinesia in Parkinson's disease: mechanisms and current non-pharmacological interventions. J Neurochem. 2014;130(4):472-89. doi:10.1111/jnc.12751.
3. Polymeropoulos MH. Mutation in the a-Synuclein Gene Identified in Families with Parkinson 's disease. Science. 1997;276(5321): 2045-7. doi:10.1126/science.276.5321.2045.
4. Schiesling C, Kieper N, Seidel K, Krü ger R. Review: Familial Parkinson's disease – genetics, clinical phenotype and neuropathology in relation to the common sporadic form of the disease. Neuropathol Appl Neurobiol. 2008;34(3):255-71. doi:10.1111/j.1365-2990.2008.00952.x.
5. Shadrina MI, Slominsky PA, Limborska SA. Molecular Mechanisms of Pathogenesis of Parkinson's Disease. In: International Review Of Cell and Molecular Biology. Vol 281. 1st ed. Elsevier Inc.; 2010. P. 229-66. doi:10.1016/S1937-6448(10)81006-8.
6. Corti O, Lesage S, Brice A. What Genetics Tells us About the Causes and Mechanisms of Parkinson's Disease. Physiol Rev. 2011;91(4): 1161-218. doi:10.1152/physrev.00022.2010.
7. Lesage S, Janin S, Lohmann E, et al. LRRK2 exon 41 mutations in sporadic Parkinson disease in Europeans. Arch Neurol. 2007;64(3):425-30. doi:10.1001/archneur.64.3.425.
8. Puschmann A, Ross OA, Vilarino-Gü ell C, et al. A Swedish family with de novo alphasynuclein A53T mutation: evidence for early cortical dysfunction. Parkinsonism Relat Disord. 2009;15(9):627-32. doi:10.1016/j.parkreldis.2009.06.007.
9. Ki CS, Stavrou EF, Davanos N, et al. The Ala53Thr mutation in the alpha-synuclein gene in a Korean family with Parkinson disease. Clin Genet. 2007;71(5):471-3. doi:10.1111/j.1399-0004.2007.00781.x.
10. Krü ger R, Kuhn W, Mü ller T, et al. Ala30Pro mutation in the gene encoding alphasynuclein in Parkinson's disease. Nat Genet. 1998; 18(2):106-8. doi:10.1038/ng0298- 106.
11. Zarranz JJ, Alegre J, Gomez-Esteban JC, et al. The new mutation, E46K, of alpha- synuclein causes Parkinson and Lewy body dementia. Ann Neurol. 2004;55(2):164-73. doi:10.1002/ana.10795.
12. Kiely AP, Asi YT, Kara E, et al. A-synucleinopathy associated with G51D SNCA mutation: A link between Parkinson's disease and multiple system atrophy? Acta Neuropathol. 2013;125(5):753-69. doi:10.1007/s00401-013-1096-7.
13. Appel-Cresswell S, Vilarino-Guell C, Encarnacion M, et al. Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease. Mov Disord. 2013;28(6): 811-3. doi:10.1002/mds.25421.
14. Ikeuchi T, Kakita A, Shiga A, et al. Patients homozygous and heterozygous for SNCA duplication in a family with parkinsonism and dementia. Arch Neurol. 2008;65(4):514-9. doi:10.1001/archneur.65.4.514.
15. Sironi F, Trotta L, Antonini A, et al. Alpha-Synuclein multiplication analysis in Italian familial Parkinson disease. Parkinsonism Relat Disord. 2010;16(3):228-31. doi:10.1016/j.parkreldis.2009.09.008.
16. Шадрина МИ. Молекулярно-генетические основы болезни Паркинсона. Диcс. докт. биол. наук. Москва; 2011. 48 с. [Shadrina MI. Molecular and genetic bases of Parkinson’s disease. Diss. doct. biol. sci. Moscow; 2011. 48 p.]
17. Lill CM, Roehr JT, McQueen MB, et al. Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDgene database. PLoS Genet. 2012;8(3):4-13. doi:10.1371/journal.pgen.1002548.
18. Correia Guedes L, Ferreira JJ, Rosa MM, et al. Worldwide frequency of G2019S LRRK2 mutation in Parkinson's disease: a systematic review. Parkinsonism Relat Disord. 2010;16(4): 237-42. doi:10.1016/j.parkreldis.2009.11.004.
19. Funayama M, Hasegawa K, Kowa H, et al. A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2-q13.1. Ann Neurol. 2002;51(3):296-301.
20. Di Fonzo A, RohО CF, Ferreira J, et al. A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease. Lancet. 365(9457):412-5. doi:10.1016/S0140-6736(05)17829-5.
21. Healy DG, Falchi M, O'Sullivan SS, et al. Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study. Lancet Neurol. 2008;7(7):583-90. doi:10.1016/S1474-4422(08)70117-0.
22. Cho JW, Kim SY, Park SS, Jeon BS. The G2019S LRRK2 Mutation is Rare in Korean Patients with Parkinson's Disease and Multiple System Atrophy. J Clin Neurol. 2009;5:29-32. doi:10.3988/jcn.2009.5.1.29.
23. Nuytemans K, Meeus B, Crosiers D, et al. Relative contribution of simple mutations vs. copy number variations in five Parkinson disease genes in the Belgian population. Hum Mutat. 2009;30(7):1054-61. doi:10.1002/humu.21007.
24. Johnson J, Paisan-Ruiz C, Lopez G, et al. Comprehensive screening of a North American Parkinson's disease cohort for LRRK2 mutation. Neurodegener Dis. 2007;4(5):386-91. doi:10.1159/000105160.
25. Lesage S, Condroyer C, Lannuzel A, et al. Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson's disease. J Med Genet. 2009; 46(7):458-64. doi:10.1136/jmg.2008.062612.
26. Ross OA, Soto-Ortolaza AI, Heckman MG, et al. Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a casecontrol study. (LRRK2 exonic variants and susceptibility to Parkinson's disease). Lancet Neurol. 2011;10(10):898-908. doi:10.1016/S1474-4422(11)70175-2.LRRK2.
27. Pchelina SN, Yakimovskii AF, Emelyanov AK, et al. Screening for LRRK2 mutations in patients with Parkinson's disease in Russia: identification of a novel LRRK2 variant. Eur J Neurol. 2008;15(7):692-6. doi:10.1111/j.1468-1331.2008.02149.x.
28. Mata IF, Hutter CM, Gonzalez-Fernandez MC, et al. Lrrk2 R1441G-related Parkinson's disease: evidence of a common founding event in the seventh century in Northern Spain. Neurogenetics. 2009;10(4):347-53. doi:10.1007/s10048-009-0187-z.
29. Aasly JO, Vilarino-Gü ell C, Dachsel JC, et al. Novel pathogenic LRRK2 p.Asn1437His substitution in familial Parkinson's disease. Mov Disord. 2010;25(13):2156-63. doi:10.1002/mds.23265.
30. Chan DK, Ng PW, Mok V, et al. LRRK2 Gly2385Arg mutation and clinical features in a Chinese population with early-onset Parkinson's disease compared to late-onset patients. J Neural Transm. 2008;115(9):1275-7. doi:10.1007/s00702-008-0065-0.
31. Tan EK, Zhao Y, Skipper L, et al. The LRRK2 Gly2385Arg variant is associated with Parkinson's disease: genetic and functional evidence. Hum Genet. 2007;120(6):857-63. doi:10.1007/s00439-006-0268-0.
32. Di Fonzo A, Wu-Chou YH, Lu CS, et al. A common missense variant in the LRRK2 gene, Gly2385Arg, associated with Parkinson's disease risk in Taiwan. Neurogenetics. 2006; 7(3):133-8. doi:10.1007/s10048-006-0041-5.
33. Funayama M, Li Y, Tomiyama H, et al. Leucine-rich repeat kinase 2 G2385R variant is a risk factor for Parkinson disease in Asian population. Neuroreport. 2007;18(3):273-5. doi:10.1097/WNR.0b013e32801254b6.
34. Kim JM, Lee JY, Kim HJ, et al. The LRRK2 G2385R variant is a risk factor for sporadic Parkinson's disease in the Korean population. Parkinsonism Relat Disord. 2010;16(2): 85-8. doi:10.1016/j.parkreldis.2009.10.004.
35. Lu CS, Wu-Chou YH, van Doeselaar M, et al. The LRRK2 Arg1628Pro variant is a risk factor for Parkinson's disease in the Chinese population. Neurogenetics. 2008;9(4):271-6. doi:10.1007/s10048-008-0140-6.
36. Сапронова МР, Шнайдер НА. Эпидемиологическая и клинико-генетическая характеристика болезни Паркинсона (на примере Железногорска). Неврология, нейропсихиатрия, психосоматика. 2014;6(4):59-64. [Sapronova MR, Shnayder NA. The epidemiological, clinical, and genetic characteristics of Parkinson's disease (in case of Zheleznogorsk). Nevrologiya, neyropsikhiatriya, psikhosomatika = Neurology, neuropsychiatry, psychosomatics. 2014;6(4):59-64. (In Russ.)]. doi:10.14412/2074-2711-2014-4-59-64.
37. Pankratz N, Uniacke SK, Halter CA, et al. Genes influencing Parkinson disease onset: replication of PARK3 and identification of novel loci. Neurology. 2004;62(9):1616-8.
38. Leroy E, Boyer R, Auburger G, et al. The ubiquitin pathway in Parkinson's disease. Nature. 1998;395(6701):451-2. doi:10.1038/26652.
39. Tsika E, Glauser L, Moser R, et al. Parkinson's disease-linked mutations in VPS35 induce dopaminergic neurodegeneration. Hum Mol Genet. 2014;23(17):4621-38. doi:10.1093/hmg/ddu178.
40. Zavodszky E, Seaman MN, Moreau K, et al. Mutation in VPS35 associated with Parkinson's disease impairs WASH complex association and inhibits autophagy. Nat Commun. 2014;5(May):3828. doi:10.1038/ncomms4828.
41. Kawamoto Y, Kobayashi Y, Suzuki Y, et al. Accumulation of HtrA2/Omi in neuronal and glial inclusions in brains with alpha-synucleinopathies. J Neuropathol Exp Neurol. 2008; 67(10):984-93. doi:10.1097/NEN.0b013e31818809f4.
42. Bonifati V, Rohe CF, Breedveld GJ, et al. Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes. Neurology. 2005;65(1):87-95. doi:10.1212/01.wnl.0000167546.39375.82.
43. Di Fonzo A, Dekker MC, Montagna P, et al. FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal syndrome. Neurology. 2009;72(3):240-5. doi:10.1212/01.wnl.0000338144.10967.2b.
44. Periquet M, Latouche M, Lohmann E, et al. Parkin mutations are frequent in patients with isolated early-onset parkinsonism. Brain. 2003; 126(Pt6):1271-8.
45. Nuytemans K, Theuns J, Cruts M, Van Broeckhoven C. Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: A mutation update. Hum Mutat. 2010;31(7):763-80. doi:10.1002/humu.21277.
46. Lohmann E, Thobois S, Lesage S, et al. A multidisciplinary study of patients with earlyonset PD with and without parkin mutations. Neurology. 2009;72(2):110-6. doi:10.1212/01.wnl.0000327098.86861.d4.
47. Mullin S, Schapira A. The genetics of Parkinson's disease. Br Med Bull. 2015;114:39-52. doi:10.1093/bmb/ldv022.
48. Valente EM, Abou-Sleiman PM, Caputo V, et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science. 2004; 304(5674):1158-60. doi:10.1126/science.1096284.
49. Valente EM, Bentivoglio AR, Dixon PH, et al. Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35-p36. Am J Hum Genet. 2001;68(4):895-900. doi:10.1086/319522.
50. Ibanez P, Lesage S, Lohmann E, et al. Mutational analysis of the PINK1 gene in early- onset parkinsonism in Europe and North Africa. Brain. 2006;129(Pt3):686-94. doi:10.1093/brain/awl005.
51. Bonifati V, Rizzu P, van Baren MJ, et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science. 2003;299(5604):256-9. doi:10.1126/science.1077209.
52. Tang B, Xiong H, Sun P, et al. Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease. Hum Mol Genet. 2006;15(11):1816-25. doi:10.1093/hmg/ddl104.
53. Canet-Aviles RM, Wilson MA, Miller DW, et al. The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic aciddriven mitochondrial localization. Proc Natl Acad Sci U S A. 2004;101(24):9103-8. doi:10.1073/pnas.0402959101.
54. Williams DR, Hadeed A, Al-Din AS, et al. Kufor Rakeb disease: autosomal recessive, levodopa- responsive parkinsonism with pyramidal degeneration, supranuclear gaze palsy, and dementia. Mov Disord. 2005;20(10):1264-71. doi:10.1002/mds.20511.
55. Ning YP, Kanai K, Tomiyama H, et al. PARK9-linked parkinsonism in eastern Asia: mutation detection in ATP13A2 and clinical phenotype. Neurology. 2008;70(16 Pt 2):1491-3. doi:10.1212/01.wnl.0000310427.72236.68.
56. Di Fonzo A, Chien HF, Socal M, et al. ATP13A2 missense mutations in juvenile parkinsonism and young onset Parkinson disease. Neurology. 2007;68(19):1557-62. doi:10.1212/01.wnl.0000260963.08711.08.
57. Ramirez A, Heimbach A, Grü ndemann J, et al. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet. 2006;38(10):1184-91. doi:10.1038/ng1884.
58. Kono S, Shirakawa K, Ouchi Y, et al. Dopaminergic neuronal dysfunction associated with parkinsonism in both a Gaucher disease patient and a carrier. J Neurol Sci. 2007;252(2): 181-4. doi:10.1016/j.jns.2006.10.019.
59. Ганькина ОА. Клинико-нейропсихологические особенности болезни Паркинсона у носителей мутации гена глюкоцереброзидазы А. Диcс. канд мед. наук. Москва; 2016. 102 с. [Gan'kina OA. Clinical and neuropsychological features of Parkinson’s disease in gene glucocerebrosidase A mutation carrier. Diss. cand. med. sci. Moscow; 2016. 102 p.]
Review
For citations:
Tappakhov A.A., Popova T.E., Nikolaeva T.Y., Gurieva P.I., Shnaider N.A., Petrova M.M., Sapronova M.R. The genetic basis of Parkinson's disease. Neurology, Neuropsychiatry, Psychosomatics. 2017;9(1):96-100. (In Russ.) https://doi.org/10.14412/2074-2711-2017-1-96-100
Views: 572
Email this article 