Using global team science to identify genetic Parkinson's disease worldwide.

Fue publicado el artículo en el que participa Uruguay:

Ann Neurol. 2019 Jun 2. doi: 10.1002/ana.25514. [Epub ahead of print]

Using global team science to identify genetic Parkinson's disease worldwide.

Vollstedt EJ1, Kasten M1,2, Klein C1; MJFF Global Genetic Parkinson's Disease Study Group.

Collaborators (209)
Aasly J, Adler C, Ahmad-Annuar A, Albanese A, Alcalay R, Al-Mubarak B, Alvarez V, Andree-Muñoz B, Annesi G, Appel-Cresswell S, Arkadir D, Armasu S, Barber TR, Bardien S, Barkhuizen M, Barrett MJ, BaŞak AN, Beach T, Benitez BA, Berg D, Bhatia K, Binkofski F, Blauwendraat C, Bonifati V, Borges V, Bozi M, Brice A, Brighina L, Brockmann K, Brüggemann N, Camacho M, Cardoso F, Belin AC, Carr J, Chan P, Chang-Castello J, Chase B, Chen-Plotkin A, Chung SJ, Cilia R, Clarimon J, Clark L, Cornejo-Olivas M, Corvol JC, Cosentino C, Cras P, Crosiers D, Damásio J, Das P, de Carvalho Aguiar P, De Michele G, De Rosa A, Dieguez E, Dorszewska J, Erer S, Ertan S, Farrer M, Fedotova E, Ferese R, Ferrarese C, Ferraz H, Fiala O, Foroud T, Friedman A, Frigerio R, Funayama M, Gambardella S, Garraux G, Gatto EM, Genç G, Goldwurm S, Gomez-Esteban JC, Gómez-Garre P, Gorostidi A, Grosset D, Hanagasi H, Hardy J, Hassan A, Hattori N, Hauser RA, Hedera P, Hentati F, Hertz JM, Holton JL, Houlden H, Hutz MH, Ikeuchi T, Illarioshkin S, Inca-Martinez M, Infante J, Jankovic J, Jeon BS, Jesús S, Jimenez-Del-Rio M, Kasten M, Kataoka H, Kawakami H, Kim YJ, Klein C, Klivényi P, Koks S, König IR, KostiĆ V, Koziorowski D, Krüger R, Krygowska-Wajs A, Kulisevsky J, Lang A, LeDoux M, Lesage S, Lim SY, Lin CH, Lohmann K, Lopera F, Lopez G, Lu CS, Lynch T, Machaczka M, Madoev H, Magalhães M, Majamaa K, Maraganore D, Marder K, Markopoulou K, Martikainen MH, Mata I, Mazzetti P, Mellick G, Menéndez-González M, Micheli F, Mirelman A, Mir P, Morino H, Morris H, Munhoz RP, Naito A, Olszewska DA, Ozelius LJ, Padmanabhan S, Paisán-Ruiz C, Payami H, Peluso S, Petkovic S, Petrucci S, Pezzoli G, Pimentel M, Pirker W, Pramstaller PP, Pulkes T, Puschmann A, Quattrone A, Raggio V, Ransmayr G, Rieder C, Riess O, Rodriguez-Porcel F, Rogaeva E, Ross OA, Ruiz-Martinez J, Sammler E, Luciano MS, Satake W, Saunders-Pullman R, Sazci A, Scherzer C, Schrag A, Schumacher-Schuh A, Sharma M, Sidransky E, Singleton AB, Petersen MS, Smolders S, Spitz M, Stefanis L, Struhal W, Sue C, Swan M, Swanberg M, Taba P, Taipa R, Tan M, Tan AH, Tan EK, Tang B, Tayebi N, Thaler A, Thomas A, Toda T, Toft M, Torres L, Tumas V, Valente EM, Van Broeckhoven C, Vecsei L, Velez-Pardo C, Vidailhet M, Vollstedt EJ, Warner TT, Williams-Gray CH, Winkelmann J, Woitalla D, Wood NW, Wszolek ZK, Wu RM, Wu YR, Xie T, Yoshino H, Zhang B, Zimprich A.

Author information
1
Institute of Neurogenetics, University of Luebeck, Luebeck, Germany.
2
Department of Psychiatry, University of Luebeck, Luebeck, Germany.


https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.25514

Variable frequency of LRRK2 variants in the Latin American research consortium on the genetics of Parkinson’s disease (LARGE-PD), a case of ancestry

Salió la publicación con los resultados de LARGE-PD para mutaciones en LRRK2 en Latinoamérica del que somos participantes. A continuación tienen el resumen y siguiendo el link se accede al artículo completo.


Variable frequency of LRRK2 variants in the Latin American research consortium on the genetics of Parkinson’s disease (LARGE-PD), a case of ancestry

Mario Cornejo-Olivas1,2, Luis Torres3,4, Mario R. Velit-Salazar1,5, Miguel Inca-Martinez1, Pilar Mazzetti1,4, Carlos Cosentino3,4,Federico Micheli6, Claudia Perandones6, Elena Dieguez7, Victor Raggio8, Vitor Tumas9, Vanderci Borges10, Henrique B. Ferraz10,Carlos R. M. Rieder11, Artur Shumacher-Schuh11, Carlos Velez-Pardo12, Marlene Jimenez-Del-Rio12, Francisco Lopera12,Jorge Chang-Castello13, Brennie Andreé-Munoz14, Sarah Waldherr15,16, Dora Yearout15,16, Cyrus P. Zabetian15,16and Ignacio F. Mata15,16

1Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru;2Northern Pacific Global Health Research Training Consortium, Bethesda, MD, USA;3Movement Disorders Unit, Instituto Nacional de Ciencias Neurologicas, Lima, Peru;4Universidad Nacional Mayor de San Marcos, Lima, Peru;5Universidad Peruana CayetanoHeredia, Lima, Peru;6Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Buenos Aires, Argentina;7Neurology Institute, Universidad de la Republica,Montevideo, Uruguay;8Department of Genetics, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay;9Ribeirão Preto Medical School, Universidade de SãoPaulo, Ribeirão Preto, Brazil;10Movement Disorders Unit, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo, SP, Brazil;11Hospital deClínicas de Porto Alegre, Porto Alegre, Brazil;12Neruroscience Research Group, Medical Research Institute, Universidad de Antioquia, Medellin, Colombia;13Department ofGenetics, School of Medici ne, Universidad de Guayaquil, Hospital Luis Vernaza, Guayaquil, Ecuador;14Service of Neurology, Hospital Luis Vernaza, Guayaquil, Ecuador;15VeteransAffairs Puget Sound Health Care System, University of Washington, Seattle, WA, USA and16Department of Neurology, University of Washington, Seattle, WA, USACorrespondence: Ignacio F . Mata (nachofm@uw.edu)

Mutations in Leucine Repeat Rich Kinase 2 (LRRK2), primarily located in codons G2019 and R1441, represent the most common genetic cause of Parkinson’s disease in European-derived populations. However, little is known about the frequency of these mutations in Latin American populations. In addition, a prior study suggested that a LRRK2 polymorphism (p.Q1111H) specific to Latino and Amerindian populations might be a risk factor for Parkinson’s disease, but this finding requires replication. We screened1734 Parkinson’s disease patients and 1097 controls enrolled in the Latin American Research Consortium on the Genetics of Parkinson’s disease (LARGE-PD), which includes sites in Argentina, Brazil, Colombia, Ecuador, Peru, and Uruguay. Genotypes were determined by TaqMan assay (p.G2019S and p.Q1111H) or by sequencing of exon 31 (p.R1441C/G/H/S). Admixture proportion was determined using a panel of 29 ancestry informative markers. We identified a total of 29 Parkinson’s disease patients (1.7%) who carried p.G2019S and the frequency ranged from 0.2% in Peru to 4.2% in Uruguay. Only two Parkinson’s disease patients carried p.R1441G and one patient carried p.R1441C. There was no significant difference in the frequency of p.Q1111H in patients (3.8%) compared to controls (3.1%; OR 1.02, p = 0.873). The frequency of LRRK2-p.G2019S varied greatly between different Latin American countries and was directly correlated with the amount of European ancestry observed. p.R1441G is rare in Latin America despite the large genetic contribution made by settlers from Spain, where the mutation is relatively common.
npj Parkinson’s Disease  (2017) 3:19  ; doi:10.1038/s41531-017-0020-6

http://rdcu.be/tb39

Parkinson’s disease: From human genetics to clinical trials

Parkinson’s disease: From human genetics to clinical trials

Marcel P. van der Brug1, Andrew Singleton2, Thomas Gasser3 and Patrick A. Lewis4,5,6,*

Science Translational Medicine  16 Sep 2015:
Vol. 7, Issue 305, pp. 205ps20
DOI: 10.1126/scitranslmed.aaa8280

Juvenile Huntington’s Disease: The Cruel Mutation

Juvenile Huntington’s Disease: The Cruel Mutation

Un buen resumen del estado del arte en Investigación en Enfermedad de Parkinson

http://spittoon.23andme.com/2012/04/09/the-state-of-the-science-of-parkinsons-research/

Genética y Enfermedad de Parkinson

Un excelente artículo para entender las bases de la investigación en genética de la EP (en inglés) en la web de la Parkinson´s Disease Foundation:

Genetics: A Foundation for Future Parkinson's Treatments por Matthew Farrer.

Revisión sobre Genética de la Enfermedad de Parkinson

Nuestros colegas y amigos del Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System de Seattle,USA, han publicado recientemente este completo y actualizado análisis de los genes vinculados a EP.
J Geriatr Psychiatry Neurol. 2010 Dec;23(4):228-42.

Análisis genético de vías patogénicas a la EP

Artículo de revisión de John Hardy, Neuron 2010;68:201-206.

PARK 14

Yoshino H, Tomiyama H, Tachibana N, Ogaki K, Li Y, Funayama M, Hashimoto T, Takashima S, Hattori N. Phenotypic spectrum of patients with PLA2G6 mutation and PARK14-linked parkinsonism. Neurology. 2010 Oct 12;75(15):1356-61.

Avances en patogenia de la EP

Recientemente fue publicado el comentario:

Rejko Krüger, LRRK2 in Parkinson's disease – drawing the curtain of penetrance: a commentary, BMC Medicine 2008, 6:33.

Sobre el trabajo:

Latourelle JC, Sun M, Lew MF, Suchowersky O, Klein C, Golbe LI, Mark MH, Growdon JH, Wooten F, et al.: The G2019S mutation in LRRK2 is not fully penetrant: The GenePD study. BMC Medicine 2008; 6:32.

Se trata de una excelente y breve revisión de la genética de la EP en general y de la asociada a la mutación G2019S del gene LRRK2. El autor comenta el trabajo mencionado, que muestra una penetrancia incompleta de esta mutación y un efecto de genes modificadores del efecto de la misma. Muestra como la complejidad etiológica y de los mecanismos que llevan a la EP se va desentrañando a partir de los estudios de genética molecular.

Otro excelente trabajo que colabora en este sentido es:

Aaron D Gitler, Alessandra Chesi, Melissa L Geddie, Katherine E Strathearn, Shusei Hamamichi, Kathryn J Hill et al, a-Synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity, Nature Genetics 2008; doi:10.1038/ng.300.

En el mismo, los autores analizan las interacciones proteicas de la alfa sinucleína con otra de las proteínas involucradas en la EP: ATP13A2 (PARK9). Además muestran el efecto de la alfa sinucleína como protectora sobre la exposición al manganeso (reportado como un factor ambiental que favorece la aparicion de EP).

Mutaciones y EP en Uruguay primeros datos

Recientemente se han publicado los primeros estudios moleculares en pacientes uruguayos con EP. Los primeros resultados muestran que casi un 5% de los pacientes urguayos de EP tienen una de las dos mutaciones frecuentes en el gene LRRK2 (PARK8).


Parkinsonism Relat Disord. 2008 Nov 1.

LRRK2 mutations in patients with Parkinson's disease from Peru and Uruguay.

Mata IF, Cosentino C, Marca V, Torres L, Mazzetti P, Ortega O, Raggio V, Aljanati R, Buzó R, Yearout D, Dieguez E, Zabetian CP.

Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA; Department of Neurology, University of Washington, Seattle, WA, USA.

Variation in the leucine-rich repeat kinase 2 (LRRK2) gene represents the most common genetic determinant of Parkinson's disease (PD) identified to date. While the frequency and distribution of LRRK2 mutations have been well-studied in Europe and North America, few data are available from South America. To address this gap in knowledge, we screened two cohorts of patients with PD from Peru (n=240) and Uruguay (n=125) for the three most common LRRK2 mutations (R1441C, R1441G, G2019S). We identified at total of seven patients with mutations, one with R1441G, and six with G2019S. The carrier frequency was significantly greater in the Uruguayan cohort (4.8%) than in the Peruvian cohort (0.4%; p=0.007). This likely resulted from a greater admixture proportion in the Peruvian sample. Haplotype analyses suggested that G2019S was probably brought to Peru and Uruguay by European settlers. In contrast, the origin of R1441G in our cohort was not clear, as the patient with this mutation had a background haplotype that was clearly distinct from that reported in carriers from Europe and North America. Our data add to a growing body of evidence indicating that LRRK2 mutations are widely distributed across South America but might differ by region in prevalence.