Identification and haplotype analysis of LRRK2 G2019S in Japanese patients with Parkinson disease

Department of Neuropsychiatry, Okayama University, Okayama, Okayama, Japan
Neurology (Impact Factor: 8.3). 09/2006; 67(4):697-9. DOI: 10.1212/01.wnl.0000227732.37801.d4
Source: PubMed

ABSTRACT LRRK2 G2019S is the most common known cause of Parkinson disease (PD) in patients of European origin, but little is known about its distribution in other populations. The authors identified two of 586 Japanese patients with PD heterozygous for the mutation who shared a haplotype distinct from that observed in Europeans. This suggests that G2019S originated from separate founders in Europe and Japan and is more widely dispersed than previously recognized.

  • [Show abstract] [Hide abstract]
    ABSTRACT: La malattia di Parkinson è la seconda patologia neurodegenerativa per frequenza ed è caratterizzata da una perdita progressiva dei neuroni dopaminergici e da un accumulo di corpi di Lewy. In questi ultimi 10 anni l’identificazione di almeno 13 loci e 9 geni (Parkina, PINK1, DJ-1, ATP13A2, SNCA, UCHL1, LRRK2, GIGYF2 e Omi/HTRA2) implicati nelle forme familiari e sporadiche del morbo di Parkinson ha permesso di comprendere meglio la fisiopatologia di questa complessa entità. Le forme monogeniche hanno una frequenza variabile a seconda dell’origine etnica delle popolazioni studiate. Un effetto di dose del gene è osservato per il gene SNCA e il fenotipo dei portatori delle mutazioni è spesso quello di una sindrome parkinsoniana tipica. La penetranza di alcune mutazioni dipende dall’età e, a volte, è incompleta. Alcuni geni implicati nelle forme monogeniche della malattia di Parkinson sono anche fattori di rischio in alcuni casi sporadici.
    01/2010; 10(2):1–9. DOI:10.1016/S1634-7072(10)70497-9
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Neurobiology of Aging 06/2014; 35(11). DOI:10.1016/j.neurobiolaging.2014.05.025 · 4.85 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Leucine-rich repeat kinase 2 (LRRK2, PARK8) gene has attracted considerable attention since the variants in this gene are recognized as the most common cause of Parkinson's disease (PD) so far. A number of association studies concerning variants of LRRK2 gene and PD susceptibility have been conducted in various populations. However, some results were inconclusive. To derive a more precise estimation of the relationship between LRRK2 and genetic risk of PD, we performed a comprehensive meta-analysis which included 27,363 cases and 29,741 controls from 61 published case-control studies. Totally, the effect of five LRRK2 variants all within the coding regions, i.e. G2019S, G2385R, R1628P, P755L and A419V, were evaluated in the meta-analysis using fixed effect model or random effects model if heterogeneity existed. There were genetic associations between four variants (G2019S, G2385R, R1628P and A419V) and increased PD risk, while there was no evidence of statistically significant association between P755L and PD. Publication bias and heterogeneity were absent in most analyses. Within its limitations, this meta-analysis demonstrated that the G2019S, G2385R, R1628P and A419V variations are risk factors associated with increased PD susceptibility. However, these associations vary in different ethnicities.
    Parkinsonism & Related Disorders 05/2012; 18(6):722-30. DOI:10.1016/j.parkreldis.2012.04.013 · 4.13 Impact Factor