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

Mata, Ignacio; Cosentino, Carlos; Marca, Victoria; Torres, Luís; Mazzetti, Pilar; Ortega, Olimpio; Raggio, Víctor; Aljanati, R.; Buzó, Ricardo; Yearout, Dora; Diéguez, Elena; Zabetian, Cyrus P.

doi:10.1016/j.parkreldis.2008.09.002

Cited by 37 publications

(44 citation statements)

References 25 publications

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“…Three exons of LRRK2 that have been frequently reported to contain PD-associated mutations (exons 31, 41, and 48) were analyzed by polymerase chain reaction-direct sequencing using the Big Dye Terminator v.1.1 Cycle Sequencing Kit (Life Technologies, Foster City, CA, USA) as previously described (Zimprich et al, 2004). Haplotype analysis of LRRK2 flanking region was performed using previously described methods (Mata et al, 2005, 2009a, 2009b). …”

Section: Methodsmentioning

confidence: 99%

“…However, p.R1441G carriers are extremely rare outside of Spain (Haugarvoll and Wszolek, 2009; Mata et al, 2005, 2009b; Simon-Sanchez et al, 2006). To date, only 4 probands with p.R1441G outside of northern Spain have been reported (Cornejo-Olivas et al, 2013; Deng et al, 2006; Mata et al, 2009a; Yescas et al, 2010). Interestingly, most of the reported p.R1441G PD patients share a common founder, and this mutation is regarded as a rare haplotype (Haugarvoll and Wszolek, 2009; Mata et al, 2005, 2009b; Simon-Sanchez et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Identification of a Japanese family with LRRK2 p.R1441G-related Parkinson's disease

Hatano

Funayama

Kubo

et al. 2014

Neurobiology of Aging

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Leucine-rich repeat kinase 2 (LRRK2) is a causative gene of autosomal dominant familial Parkinson’s disease (PD). We screened for LRRK2 mutations in 3 frequently reported exons (31, 41, and 48) in our cohort of 871 Japanese patients with PD (430 with sporadic PD and 441 probands with familial PD). Direct sequencing analysis of LRRK2 revealed 1 proband (0.11%) with a p.R1441G mutation, identified for the first time in Asian countries, besides frequently reported substitutions including, the p.G2019S mutation (0.11%) and p.G2385R variant (11.37%). Several studies have suggested that the LRRK2 p.R1441G mutation, which is highly prevalent in the Basque country, is extremely rare outside of northern Spain. Further analysis of family members of the proband with the p.R1441G mutation revealed that her mother and first cousin shared the same mutation and parkinsonism. Haplotype analysis revealed a different haplotype from that of the original Spanish families. Our patients demonstrated levodopa-responsive parkinsonism with intrafamilial clinical heterogeneity. This is the first report of familial PD because of the LRRK2 p.R1441G mutation in Asia.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of a Japanese family with LRRK2 p.R1441G-related Parkinson's disease

Hatano

Funayama

Kubo

et al. 2014

Neurobiology of Aging

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“…La mutación G2019S en el gen LRRK2, considerada la mutación dominante más frecuente en población caucásica, fue reportada con muy baja frecuencia en una población de pacientes con EP peruanos (22) ; 2). El hallazgo inesperado de la alta frecuencia del polimorfismo Q1111H en el gen LRRK2 en población mestiza peruana, permitió desestimar este polimorfismo como un factor de riesgo para EP (23) ; 3).…”

Section: Investigación En Otras Enfermedades Monogénicas Y Desordenesunclassified

Neurogenética en el Perú, ejemplo de investigación traslacional

Mazzetti

Inca‐Martinez²,

Tirado-Hurtado³

et al. 2015

Rev Peru Med Exp Salud Publica

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RESUMENLa neurogenética es una disciplina emergente en el Perú que vincula la investigación básica con la práctica clínica. El Centro de Investigación Básica en Neurogenética, es el único centro en el Perú dedicado a la atención especializada de enfermedades neurogenéticas. La investigación en esta área está estrechamente ligada a la enfermedad de Huntington, desde la genotipificación del gen HTT por PCR, hasta los actuales estudios de haplogrupos en esta enfermedad. La investigación en otras enfermedades monogénicas permitió la implementación de metodologías alternativas para la genotipificación del síndrome X frágil y distrofia miotónica tipo 1. Esfuerzos colaborativos nacionales e internacionales han permitido conocer nuevas variantes genéticas en enfermedades complejas, como la enfermedad de Parkinson y Alzheimer. El entrenamiento multidisciplinario y la mentoría fomentan la formación de nuevos especialistas en neurogenética, permitiendo el crecimiento sostenido de esta disciplina en el país. El impulso de la investigación en el Perú ha impulsado el crecimiento de la investigación en neurogenética; sin embargo, las limitaciones en infraestructura, tecnología y capacitación aún son un reto para el crecimiento de investigación en esta disciplina. Palabras clave: Investigación traslacional; Neurología; Genética (fuente: DeCS BIREME). NEUROGENETICS IN PERU, EXAMPLE OF TRANSLATIONAL RESEARCH ABSTRACTNeurogenetics is an emerging discipline in Peru that links basic research with clinical practice. The Neurogenetics Research Center located in Lima, Peru is the only unit dedicated to the specialized care of neurogenetic diseases in the country. From the beginning, neurogenetics research has been closely linked to the study of Huntington's Disease (HD), from the PCR genotyping of the HTT gene, to the current haplogroup studies in HD. Research in other monogenic diseases led to the implementation of alternative methodologies for the genotyping of Fragile X and Myotonic Dystrophy Type 1. Both, national and international collaborative efforts have facilitated the discovery of new genetic variants in complex multigenic diseases such as Parkinson's disease and Alzheimer's disease. Additionally, multidisciplinary education and mentoring have allowed for the training of new neurogenetics specialists, supporting the sustained growth of the discipline in the country. The promotion of research in Peru has spurred the growth of neurogenetics research, although limitations in infrastructure, technology, and education remain a challenge for the further growth of research in this field.

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“…Frequencies ranged from the no cases to 35.7% in sporadic and 42% in familial North-African Arab patients (Brás et al 2005;Lesage et al 2005Lesage et al , 2006Lesage et al , 2008Clark et al 2006;Deng et al 2006;Gaig et al 2006;Goldwurm et al 2006;Infante et al 2006;Ozelius et al 2006;Marongiu et al 2006;Mata et al 2006Mata et al , 2009bCivitelli et al 2007;Cossu et al 2007;Ferreira et al 2007;González-Fernández et al 2007;Ishihara et al 2007;Orr-Urtreger et al 2007;Perez-Pastene et al 2007;Squillaro et al 2007;Hulihan et al 2008;Munhoz et al 2008;Pimentel et al 2008;Correia Guedes et al 2009;De Rosa et al 2009;Floris et al 2009;Gorostidi et al 2009). …”

Section: Discussionmentioning

confidence: 99%

Analysis of Leucine-rich repeat kinase 2 (LRRK2) and Parkinson protein 2 (parkin, PARK2) genes mutations in Slovak Parkinson disease patients

Bognár¹,

Baldovič²,

Benetin³

et al. 2013

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Abstract. Parkinson disease (PD) is a chronic neurodegenerative movement disorder characterized by selective loss of nigrostriatal dopaminergic neurons and formation of Lewy bodies. Clinical manifestations include motor impairments involving tremor, bradykinesia, postural instability and rigidity.Using dHPLC method we screened exons 31, 35, 41, 48 of the Leucine-rich repeat kinase 2 (LRRK2) gene and exons 2, 6 and 7 of Parkinson protein 2 (parkin, PARK2) genes in a cohort of 216 consecutive, unrelated Slovak patients with familial or sporadic PD, including early and late onset. By this means we aimed to detect the most common pathogenic mutations within LRRK2 (Arg1441Cys, Arg1441Gly, Arg1628Pro, Tyr1699Cys, Gly2019Ser, Ile2020Thr, Gly2385Arg) and parkin genes responsible for late and early onset forms of disease, respectively. However, none of these mutations was identified in our cohort. Heterozygous point mutation p.Arg275Trp in exon 7 of parkin gene was identified in one patient with age at onset 61 years. Furthermore, we observed the presence of one exonic (LRRK2 ex 48: 7155A>G) and eight intronic polymorphisms (in LRRK2: IVS35+23T>A, IVS47-91insGCCAT, IVS47-91insGCAT, IVS47-41A>G, IVS47-9delT, IVS47-20C>T, IVS47-90A>G, in parkin: IVS2+25T>C), three of which were novel.

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

Cited by 37 publications

References 25 publications

Identification of a Japanese family with LRRK2 p.R1441G-related Parkinson's disease

Identification of a Japanese family with LRRK2 p.R1441G-related Parkinson's disease

Neurogenética en el Perú, ejemplo de investigación traslacional

Analysis of Leucine-rich repeat kinase 2 (LRRK2) and Parkinson protein 2 (parkin, PARK2) genes mutations in Slovak Parkinson disease patients

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