A common LRRK2 mutation in idiopathic Parkinson's disease

Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

“…This mutation is responsible for both familial (4% worldwide) and apparently sporadic (1% worldwide) PD cases, and has a very low frequency in healthy populations (<0.1% worldwide) [194, 205Ͳ207]. Particularly, most patients with the G2019S mutation exhibitedalphaͲsynͲpositive LBs as in sporadic PD [206,208,209]. Tong et al(2010) [210], showed that accumulation and aggregation of alphaͲsyn and ubiquitinated proteins occurred in aged LRRK2 germͲline deletion mice with great loss of LRRK2.…”

Comprehensive mutational analysis of LRRK2 reveals variants supporting association with autosomal dominant Parkinson's disease

“…7,9,25 Considering that p.G2019S is the most frequent among the known mutations, the overall clinical presentation of patients with LRRK2 mutations may largely reflect that of patients with p.G2019S. Interestingly, a previously reported case of a patient with the p.S1228T mutation, located in the same exon and domain as in p.N1221K, showed a similarly early age at onset to the patient with p.N1221K, who developed symptoms at the age of 49.…”

“…In Caucasians, p.G2019S is the most frequent in both Ad-PD and sPD, accounting for B5% of Ad-PD patients and 1.6% of sPD patients. 8,9,18 Many of the patients from European populations share a common haplotype, suggesting that they have a common founder originating in the Near East at least 4000 years ago. 19,20 In contrast, no single mutation has been reported as being predominant in Asian populations.…”

“…Analysis of the entire 51 exons of LRRK2 by the conventional direct nucleotide sequencing method, however, is very laborious. Therefore, the majority of previous studies have focused on particular exons for mutational analysis, [8][9][10][11][12] making it difficult to obtain accurate data on the molecular epidemiology of Ad-PD caused by LRRK2.…”

Reprint of: Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

“…This mutation is responsible for both familial (4% worldwide) and apparently sporadic (1% worldwide) PD cases and has a very low frequency in healthy populations (o 0.1% worldwide) [194,205-"207]. Particularly, most patients with the G2019S mutation exhibited a-syn-positive LBs as in sporadic PD [206,208,209]. Tong et al [210] showed that accumulation and aggregation of a-syn and ubiquitinated proteins occurred in aged LRRK2 germ-line deletion mice with great loss of LRRK2.…”