ABSTRACT
Introduction: Mutations in the leucine-rich repeat kinase 2 gene (LRRK2 or Dardarin) are considered to be a common cause of autosomal dominant and sporadic Parkinson's disease, but the prevalence of these mutations varies among populations. Objective: To analyzed the frequency of the LRRK2 p.G2019S mutation (c.6055G>A transition) in a sample of Colombian patients. Methods: In the present study we have analyzed the frequency of the LRRK2 p.G2019S mutation in 154 patients with familial or sporadic Parkinson Disease, including early and late onset patients, and 162 normal controls. Results: Our results show occurrence of this mutation in two cases (2/154, 1.3%) with classical Parkinson's signs, and one completely asymptomatic control (1/162, 0.6%). Conclusion: The p.G2019S mutation is not an important causal factor of Parkinson Disease in Colombia having similar frequencies to those reported in other Latin American populations.
Introducción: Las mutaciones en el LRRK2 (del inglés gen leucinerich repeat kinase 2) o Dardarina se consideran una causa común de enfermedad de Parkinson autosómica dominante. Sin embargo, la prevalencia de estas mutaciones varia en diferentes poblaciones. Objetivo: Snalizar la frecuencia de la mutación p.G2019S (transición c.6055 G>A) del gen LRRK2en una muestra de pacientes colombianos. Métodos: En el presente estudio analizamos la frecuencia de la mutación en 154 pacientes con enfermedad de Parkinson familiar o esporádica, y 162 controles normales. Resultados: Se determinó la presencia de la mutación en 2 casos de Parkinson (2/154, 1.3%) los cuales presentan los signos clásicos de la enfermedad y en un control completamente asintomático (1/162, 0.6%). Conclusión: La mutación p.G2019S no es un factor causal importante de la Enfermedad de Parkinson en la población Colombiana, y muestra frecuencias similares a las reportadas en otras poblaciones latinoamericanas.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Gene Frequency , Parkinson Disease/genetics , Protein Serine-Threonine Kinases/genetics , Age of Onset , Case-Control Studies , Colombia , Genetic Predisposition to Disease , Mutation , Parkinson Disease/physiopathologyABSTRACT
Aim: Many causative genes and susceptibility loci have been identified to be associated with Parkinson's disease (PD) in different ethnic populations. One of these genes is the Leucin-rich repeat kinase 2 (LRRK2) gene. The G2019S substitution in that gene is the most common mutation identified to co-segregates with PD. In the North part of Egypt (Alexandria and nearby region), an incidence of 9.7% of heterozygous mutation in LRRK2 G2019S was reported in a sample of Egyptians with sporadic PD. We investigated the same mutation in 69 Egyptian patients with sporadic PD and 96 ethnically matched controls who all were inhabitants of Upper Egypt to find out if it could be a susceptibility gene for PD among Egyptians. Place and Duration of Study: Departments of pharmacology, neurology, and clinical pathology, Assiut University (Egypt) and Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany between June 2010 and September 2011. Methodology: Sixty nine patients with PD of sporadic type and ninety six controls were included in the study and all were inhabitants of Assiut Governorate and nearby region in Upper Egypt. PCRgenotyping analysis for the point mutation G2019S in the exon 41 was performed and presence or absence of mutation was confirmed by direct sequencing of the probands identified of the DNA. Results: Genotyping analysis and sequencing of DNA showed only one patient who was carrier to the mutation G2019S (1/69; incidence: 1.45%) and it was of heterozygous style. The rest of subjects (patients and control) were not carrying the mutation. This rarity of this kind of mutation among the Egyptian sample studied suggests that it may be a rare cause of PD in Upper Egypt region. However, if it is observed, it may have a trend of heterozygosity genotyping style as previously defined in the Egyptians living in the North region of Egypt Conclusion: The very low incidence of G2019S mutation in Egyptians living in Upper Egypt compared to Egyptians inhabitants in North Egypt suggests a multicenter study on a large number of Egyptians with Parkinson’s disease to reach a real incidence of that mutation and if it has (or not) a correlation to causation and course of Parkinson’s disease among Egyptians.
ABSTRACT
BACKGROUND AND PURPOSE: The LRRK2 (PARK8; OMIM607060) substitution was recently identified as a causative mutation for Parkinson's disease (PD). The pathologic heterogeneity of LRRK2-positive patients suggests that mutation of the LRRK2 gene is associated with the pathogenesis of PD and Parkinson-plus disorders, such as multiple system atrophy (MSA). We previously reported that the G2019S LRRK2 mutation-which is the most common LRRK2 mutation-was not found in a sample of 453 Korean PD patients. In the present study, we extended the screening for the G2019S mutation to a larger group of PD and MSA patients. METHODS: We performed a genetic analysis of the G2019S mutation in 877 patients with PD and 199 patients with MSA using a standard PCR and restriction digestion method. RESULTS: None of the subjects carried the G2019S mutation. CONCLUSIONS: The results of the present study support that the G2019S mutation is extremely rare in PD and is unlikely to be associated with MSA in the Korean population.