Keywords
Parkinson’s disease
Mutation
Neurons
Mutation
Neurons
How to Cite
Castañeda-Garzón, S. A., Urrego-Duque, L. F., & Sánchez-Corredor, M. C. (2017). Molecular variants in gene PARK2 in Colombian patients with Parkinson’s disease. Pilot study between 2013 and 2014. Médicas UIS, 30(3), 31–8. https://doi.org/10.18273/revmed.v30n3-2017003
Abstract
Introduction: parkinson’s disease is characterized by the degeneration and loss of dopaminergic neurons in the brain. There are genetic factors involved in its development in its early onset form, such as the PARK2 gene encoding the parkin, an E3 ubiquitin ligase, which in the case of mutations loses its ability to regulate protein degradation causing stress and cell death. Objective: to determine the presence of molecular changes in PARK2 exons 3, 4 and 5 in a group of 29 patients and 21 colombian controls with early onset Parkinson’s disease or a family history of Parkinson’s disease and the possible correlation with clinical manifestations from the patients. materials and methods: observational descriptive study (between june of 2013 and november of 2014) where DNA extraction of whole blood was performed and the PCR technique was used for each of the exons. Finally, we proceeded to the automatic sequencing, analysis of the sequences with the Sequencher software and comparison with information of databases. Results: a homozygous variant (Ala46Thr) in exon 4 was identified in one patient not previously reported, possibly nonpathogenic and the Ser167Asn variant in heterozygous state in the same exon in another patient, considered pathogenic and previously reported in populations Asian and European. No variants were identified in the controls. Conclusions: changes not previously described in the colombian population, -Ala46Thr and Ser167Asn-, were identified in the group of patients and not in the controls. MÉD.UIS. 2017;30(3):31-8.
References
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23. Okubadejo N, Britton A, Crews C, Akinyemi R, Hardy J, Singleton A, et al. Analysis of Nigerians with Apparently Sporadic Parkinson Disease for Mutations in LRRK2, PRKN and ATXN3. Plos One. 2008;3(10)e3421:1-4.
24. Zhang Y, Wang ZZ, Sun HM. Lack of Association Between p.Ser167Asn Variant of Parkin and Parkinson’s Disease: A MetaAnalysis of 15 Studies Involving 2,280 Cases and 2,459 Controls. Am J Med Genet B Neuropsychiatr Genet. 2012;159B(1):38–47.
25. Miller RJ, Wilson SM. Neurological disease: UPS stops delivering! Trends Pharmacol. Sci. 2003;24(1):18-23.
26. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science. 1997; 276(5321):2045-7.
27. Gasser T. Genetics of Parkinson’s disease. Clin Genet.1998;54(4):259–65.
28. Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, et al. The ubiquitin pathway in Parkinson’s disease. Nature. 1998;395(6701):451-2.
29. Valente EM, Bentivoglio AR, Dixon PH, Ferraris A, Ialongo T, Frontali M, 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.
30. Van Duijn CM, Dekker MC, Bonifati V, Galjaard RJ, HouwingDuistermaat JJ, Snijders PJ, et al. Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36. Am J Hum Genet. 2001;69(3):629-34.
31. Paisán-Ruíz C, Jain S, Evans EW, Gilks WP, Simón J, Van der Brug M, et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron. 2004;44(4):595-600.
32. Hicks AA, Pétursson H, Jónsson T, Stefánsson H, Jóhannsdóttir HS, Sainz J, et al. A susceptibility gene for late-onset idiopathic Parkinson’s disease. Ann Neurol. 2002; 52(5):549-55.
33. Pankratz N, Nichols WC, Uniacke SK, Halter C, Murrell J, Rudolph A, et al. Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families. Hum Mol Genet. 2003;12:2599–608.
2. Van der Merwe C, Carr J, Glanzmann B, Bardien S. Exonic rearrangements in the known Parkinson’s disease-causing genes are a rare cause of the disease in South African patients. Neurosci. Lett. 2016;619:168-71.
3. García S, Suárez SS, Dávalo EM, Castillo JL. Perspectiva histórica y aspectos epidemiológicos de la enfermedad de Parkinson. Med Int Mex. 2008;24(1):28-37.
4. Parkinson J. An essay on the shaking palsy. J Neuropsychiatr. Clin. Neurosci. 2002;14(2):223-36.
5. Seirafi M, Kozlov G, Gehring K. Parkin structure and function. FEBS J. 2015;282(11):2076-88.
6. Elizondo-Cárdenas G, Déctor-Carrillo MA, Martínez-Rodríguez HR, Martínez-de Villarreal L, Esmer-Sánchez MC. Genética y la enfermedad de Parkinson: Revisión de actualidades. Med. Univer. 2011;13(51):96-100.
7. Darvish H, Movafagh A, Omrani M, Firouzabadi S, Azargashb E, Jamshidi J, et al. Detection of copy number changes in genes associated with Parkinson’s disease in Iranian patients. Neurosci. Lett. 2013;551:75–8.
8. Norris K, Hao R, Chen L, Lai C, Kapur M, Shaughnessy P, et al. Convergence of Parkin, PINK1, and α-Synuclein on Stressinduced Mitochondrial Morphological Remodeling. J. Biol. Chem. 2015;290 (22):13862–74.
9. Huttenlocher J, Stefansson H, Stacy Steinberg, Helgadottir H, Sveinbjörnsdóttir S, Riess O, et al. Heterozygote carriers for CNVs in PARK2 are at increased risk of Parkinson’s disease. Hum. Mol. Genet. 2015; 24(19):5637–43.
10. Bekris LM, Mata IF, Zabetian CP. The Genetics of Parkinson Disease. J. Geriatr. Psychiatry Neurol. 2010;23(4):228–42.
11. Morris HR. Genetics of Parkinson´s disease. Ann. Med. 2005;37:86-96.
12. Ambroziak W, Koziorowski D, Kinga Duszyc K, Skoczylas P, Chromik A, Stawek J, et al. Genomic instability in the PARK2 locus is associated with Parkinson’s disease. J. Appl Genetics. 2015;56(4):51–61.
13. Gómez-Chavarín M, Roldan-Roldan G, Morales-Espinosa R, Pérez-Soto G, Torner-Aguilar C. Mecanismos fisiopatológicos involucrados en la enfermedad de Parkinson. Arch. Neurocien. (Mex. D.F.). 2012;17(1):25-33.
14. Pineda-Trujillo N, Dulcey Cepeda A, Arias Pérez W, Moreno Masmela S, Saldarriaga Henao A, Sepúlveda Falla D, et al. Una mutación en el gen PARK2 causa enfermedad de Parkinson juvenil en una extensa familia colombiana. Iatreia. 2009;22(2):122-31.
15. Peres de Morais S. Juvenile Parkinson disease caused by parkin mutations: large deletions and pathogenic mechanisms. Disertación de maestría. Facultad de Ciencias y Tecnología de la: Universidad Nova de Lisboa. 2011.
16. Biswas A, Maulik M, Das SK, Indian Genome Variation Consortium, Ray K, Ray J. Parkin polymorphisms: risk for Parkinson’s disease in Indian population. Clin. Genet.
2007;72:484-6.
17. Asakawa S, Hattori N, Shimizu A, Shimizu Y, Minoshima S, Mizuno Y, et al. Analysis of eighteen deletion breakpoints in the parkin gene. Biochem. Biophys Res Commun. 2009;389:181-6.
18. De Rijk MC, Tzourio C, Breteler MM, Dartigues JF, Amaducci L, Lopez-Pousa S, et al. Prevalence of parkinsonism and Parkinson’s disease in Europe: the Europarkinson Collaborative Study. European Community Concerted Action on the Epidemiology of Parkinson’s Disease. J Neurol Neurosurg Psychiatry. 1997; 62(1):10-5.
19. West A, Periquet M, Lincoln S, Lücking CB, Nicholl D, Bonifati V, et al. Complex relationship between Parkin mutations and Parkinson disease. Am J Med Genet. 2002;114(5):584-91.
20. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392:605–8.
21. Sanyal J, Bhaskar LVKS, Chatterjee A, Sarkar B, Chandra Ray B, Raghavendra Rao V. Single Nucleotide Polymorphisms of PARKIN gene in ten indian populations. Antrocom Online J Anthropol. 2011;7(1):135-45.
22. Peng R, Gou Y, Yuan Q, Li T, Latsoudis H, Yuan G, et al. Mutation screening and association analysis of the arkin gene in Parkinson’s disease patients from South-West China. Eur. Neurol. 2003;49(2):85-9.
23. Okubadejo N, Britton A, Crews C, Akinyemi R, Hardy J, Singleton A, et al. Analysis of Nigerians with Apparently Sporadic Parkinson Disease for Mutations in LRRK2, PRKN and ATXN3. Plos One. 2008;3(10)e3421:1-4.
24. Zhang Y, Wang ZZ, Sun HM. Lack of Association Between p.Ser167Asn Variant of Parkin and Parkinson’s Disease: A MetaAnalysis of 15 Studies Involving 2,280 Cases and 2,459 Controls. Am J Med Genet B Neuropsychiatr Genet. 2012;159B(1):38–47.
25. Miller RJ, Wilson SM. Neurological disease: UPS stops delivering! Trends Pharmacol. Sci. 2003;24(1):18-23.
26. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science. 1997; 276(5321):2045-7.
27. Gasser T. Genetics of Parkinson’s disease. Clin Genet.1998;54(4):259–65.
28. Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, et al. The ubiquitin pathway in Parkinson’s disease. Nature. 1998;395(6701):451-2.
29. Valente EM, Bentivoglio AR, Dixon PH, Ferraris A, Ialongo T, Frontali M, 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.
30. Van Duijn CM, Dekker MC, Bonifati V, Galjaard RJ, HouwingDuistermaat JJ, Snijders PJ, et al. Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36. Am J Hum Genet. 2001;69(3):629-34.
31. Paisán-Ruíz C, Jain S, Evans EW, Gilks WP, Simón J, Van der Brug M, et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron. 2004;44(4):595-600.
32. Hicks AA, Pétursson H, Jónsson T, Stefánsson H, Jóhannsdóttir HS, Sainz J, et al. A susceptibility gene for late-onset idiopathic Parkinson’s disease. Ann Neurol. 2002; 52(5):549-55.
33. Pankratz N, Nichols WC, Uniacke SK, Halter C, Murrell J, Rudolph A, et al. Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families. Hum Mol Genet. 2003;12:2599–608.
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