Análisis de mutaciones en los genes PINK1 Y PARKIN en pacientes colombianos con enfermedad de Parkinson

Carolina Andrea Infante Molina; Laura Marlen Mora Forero; Jenny C. Ortega Rojas; Carlos E. Arboleda Bustos; William Fernández; Humberto Arboleda; Gonzalo Arboleda

doi:10.22490/24629448.993

Vol. 12 No. 21 (2014)

Published

2014-06-15

PDF (Spanish)

Metrics

Metrics Loading ...

Analysis of mutations in the genes pink1 and parkin in Colombian patients with Parkinson's disease.

DOI: https://doi.org/10.22490/24629448.993

Section

Research Article (before OJS)

Carolina Andrea Infante Molina Grupo de Neurociencias, Facultad de Medicina e Instituto de Genética, Universidad Nacional de Colombia, Universidad Colegio Mayor de Cundinamarca. Bogotá, Colombia

Laura Marlen Mora Forero Grupo de Neurociencias, Facultad de Medicina e Instituto de Genética, Universidad Nacional de Colombia, Universidad Colegio Mayor de Cundinamarca. Bogotá, Colombia

Jenny C. Ortega Rojas Grupo de Neurociencias, Facultad de Medicina e Instituto de Genética, Universidad Nacional de Colombia

Carlos E. Arboleda Bustos Grupo de Neurociencias, Facultad de Medicina e Instituto de Genética, Universidad Nacional de Colombia

William Fernández Grupo de Neurociencias, Facultad de Medicina e Instituto de Genética, Universidad Nacional de Colombia

Humberto Arboleda Grupo de Neurociencias, Facultad de Medicina e Instituto de Genética, Universidad Nacional de Colombia

Gonzalo Arboleda Grupo de Neurociencias, Facultad de Medicina e Instituto de Genética, Universidad Nacional de Colombia

Parkinson's disease is a complex neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons of the substance nigra pars compacta. It has been determined that factors both environmental and genetic contribute to its development. Mutations in the genes PINK1 and PARKIN have been associated with the early onset of disease and family history. The goal of this study was to identify mutations in the PINK1 genes (exons 4 and 6) and PARKIN (exons 2 and 7) in 22 Colombian patients with Parkinson's disease of early onset and/ or family history, by PCR amplification and sequencing. The sequences were compared with the reference consensus sequence. A homozygous change mutation was detected in the reading frame (frame shift) c.155dela in exon 2 of the PARKIN gene in a patient with early onset of the disease and family history. In addition, the presence of a polymorphism in intron 2 of the PARKIN gene was identified in seven patients, one of them in homozygous state. Mutations were not found in exons 4 and 6 of the gene PINK1. A homozygous mutation c.155dela in exon 2 of PARKIN was found in a female patient with Parkinson's disease early onset with family history. No changes to the gene PINK1 were found.

direct DNA sequencing, mutations, Parkinson's disease, PCR.

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):763-780.

Qayyum A. Etiology and Pathophysiology of Parkinson’s Disease. In: Rana AQ, ed: InTech; 2011.

Fahn S, Jankovic J, Hallett M. Chapter 5 - Current concepts on the etiology and pathogenesis of Parkinson disease. Principles and Practice of Movement Disorders 2° Edition ed. Edinburgh: W.B. Saunders; 2011:93-118.

Pradilla AG, Vesga AB, Leon-Sarmiento FE. [National neuroepidemiological study in Colombia (EPINEURO)]. Rev Panam Salud Publica. 2003;14(2):104-111.

Pankratz ND, Wojcieszek J, Foroud T. Parkinson Disease Overview. 2009.

Klein C, Lohmann-Hedrich K, Rogaeva E, Schlossmacher MG, Lang AE. Deciphering the role of heterozygous mutations in genes associated with parkinsonism. Lancet Neurol. 2007;6(7):652-662.

Camargos ST, Dornas LO, Momeni P, Lees A, Hardy J, Singleton A, et al. Familial Parkinsonism and early onset Parkinson’s disease in a Brazilian movement disorders clinic: phenotypic characterization and frequency of SNCA, PRKN, PINK1, and LRRK2 mutations. Mov Disord. 2009;24(5):662-666.

Scornaienchi V, Civitelli D, De Marco EV, Annesi G, Tarantino P, Rocca FE, et al. Mutation analysis of the PINK1 gene in Southern Italian patients with early- and late-onset parkinsonism. Parkinsonism Relat Disord. 2012;18(5):651-653.

Yonova-Doing E, Atadzhanov M, Quadri M, Kelly P, Shawa N, Musonda ST, et al. Analysis of LRRK2, SNCA, Parkin, PINK1, and DJ-1 in Zambian patients with Parkinson’s disease. Parkinsonism Relat Disord. 2012;18(5):567-571.

Thomas B, Beal MF. Parkinson’s disease. Hum Mol Genet. 2007;16 Spec No. 2:R183-194.

Wirdefeldt K, Adami HO, Cole P, Trichopoulos D, Mandel J. Epidemiology and etiology of Parkinson’s disease: a review of the evidence. Eur J Epidemiol. 2011;26 Suppl 1:S1-58.

Fung HC, Chen CM, Hardy J, Singleton AB, Lee-Chen GJ, Wu YR. Analysis of the PINK1 gene in a cohort of patients with sporadic early-onset parkinsonism in Taiwan. Neurosci Lett. 2006;394(1):33-36.

Cookson MR, Bandmann O. Parkinson’s disease: insights from pathways. Hum Mol Genet. 2010;19(R1):R21-27.

Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, et al. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet. 2000;25(3):302-305.

Zhang Y, Gao J, Chung KK, Huang H, Dawson VL, Dawson TM. Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicleassociated protein, CDCrel-1. Proc Natl Acad Sci U S A. 2000;97(24):13354-13359.

Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, et al. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol. 2010;8(1):e1000298.

Douglas J. Diagnostic criteria for Parkinson disease. . Archives of Neurology. 1999; Vol 56(1): 33-39.

Clarke CE. Parkinson’s disease. Bmj. 2007;335(7617):441-445.

Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008;79(4):368-376.

Sironi F, Primignani P, Zini M, Tunesi S, Ruffmann C, Ricca S, et al. Parkin analysis in early onset Parkinson’s disease. Parkinsonism Relat Disord. 2008;14(4):326-333.

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(6676):605-608.

Periquet M, Latouche M, Lohmann E, Rawal N, De Michele G, Ricard S, et al. Parkin mutations are frequent in patients with isolated early-onset parkinsonism. Brain. 2003;126(Pt 6):1271-1278.

Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, et al. Hereditary early-onset

Parkinson’s disease caused by mutations in PINK1. Science. 2004;304(5674):1158-1160.

Hall TA. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids Symp Ser. 1999;41:95-98.

Weckx S, Del-Favero J, Rademakers R, Claes L, Cruts M, De Jonghe P, et al. novoSNP, a novel computational tool for sequence variation discovery. Genome Res. 2005;15(3):436-442.

Abbas N, Lucking CB, Ricard S, Durr A, Bonifati V, De Michele G, et al. A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson’s Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson’s Disease. Hum Mol Genet. 1999;8(4):567-574.

Munoz E, Tolosa E, Pastor P, Marti MJ, Valldeoriola F, Campdelacreu J, et al. Relative high frequency of the c.255delA parkin gene mutation in Spanish patients with autosomal recessive parkinsonism. J Neurol Neurosurg Psychiatry. 2002;73(5):582-584.

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):122-131.

Oliveira SA, Scott WK, Nance MA, Watts RL, Hubble JP, Koller WC, et al. Association study of Parkin

gene polymorphisms with idiopathic Parkinson disease. Arch Neurol. 2003;60(7):975-980.

Solla P, Cannas A, Floris G, Murru MR, Corongiu D, Tranquilli S, et al. Parkin Exon Rearrangements and Sequence Variants in LRRK2 Mutations Carriers: Analysis on a Possible Modifier Effect on LRRK2 Penetrance. Parkinsons Dis. 2010;2010:537698.

Hoenicka J, Vidal L, Morales B, Ampuero I, Jimenez-Jimenez FJ, Berciano J, et al. Molecular findings in familial Parkinson disease in Spain. Arch Neurol. 2002;59(6):966-970.

Bras J, Guerreiro R, Ribeiro M, Morgadinho A, Januario C, Dias M, et al. Analysis of Parkinson disease patients from Portugal for mutations in SNCA, PRKN, PINK1 and LRRK2. BMC Neurol. 2008;8:1.

Dachsel JC, Mata IF, Ross OA, Taylor JP, Lincoln SJ, Hinkle KM, et al. Digenic parkinsonism: investigation of

the synergistic effects of PRKN and LRRK2. Neurosci Lett. 2006;410(2):80-84.

Rawal N, Periquet M, Lohmann E, Lucking CB, Teive HA, Ambrosio G, et al. New parkin mutations and atypical phenotypes in families with autosomal recessive parkinsonism. Neurology. 2003;60(8):1378-1381.

Okatsu K, Oka T, Iguchi M, Imamura K, Kosako H, Tani N, et al. PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria. Nat Commun. 2012;3:1016.

Tan JM, Wong ES, Lim KL. Protein misfolding and aggregation in Parkinson’s disease. Antioxid Redox Signal. 2009;11(9):2119-2134.

Johnson BN, Berger AK, Cortese GP, Lavoie MJ. The ubiquitin E3 ligase parkin regulates the

proapoptotic function of Bax. Proc Natl Acad Sci U S A. 2012;109(16):6283-6288.

Lesage S, Lohmann E, Tison F, Durif F, Durr A, Brice A. Rare heterozygous parkin variants in French early-onset Parkinson disease patients and controls. J Med Genet. 2008;45(1):43-46.

Hedrich K, Marder K, Harris J, Kann M, Lynch T, Meija- Santana H, et al. Evaluation of 50 probands with earlyonset Parkinson’s disease for Parkin mutations. Neurology. 2002;58(8):1239-1246.

Brooks J, Ding J, Simon-Sanchez J, Paisan-Ruiz C, Singleton AB, Scholz SW. Parkin and PINK1 mutations

in early-onset Parkinson’s disease: comprehensive screening in publicly available cases and control. J Med Genet. 2009;46(6):375-381.

Sun M, Latourelle JC, Wooten GF, Lew MF, Klein C, ShillHA, et al. Influence of heterozygosity for parkin mutation on onset age in familial Parkinson disease: the GenePD study. Arch Neurol. 2006;63(6):826-832.

Chung EJ, Ki CS, Lee WY, Kim IS, Kim JY. Clinical features and gene analysis in Korean patients with early-onset Parkinson disease. Arch Neurol. 2006;63(8):1170-1174.

Deng H, Le W, Shahed J, Xie W, Jankovic J. Mutation analysis of the parkin and PINK1 genes in American Caucasian early-onset Parkinson disease families. Neurosci Lett. 2008;430(1):18-22.

Infante Molina, C. A., Mora Forero, L. M., Ortega Rojas, J. C., Arboleda Bustos, C. E., Fernández, W., Arboleda, H., & Arboleda, G. (2014). Analysis of mutations in the genes pink1 and parkin in Colombian patients with Parkinson’s disease. NOVA Biomedical Sciences Journal, 12(21), 15-21. https://doi.org/10.22490/24629448.993

Download Citation

Published

Analysis of mutations in the genes pink1 and parkin in Colombian patients with Parkinson's disease.

Declaración de privacidad.

Keywords