The G2019S LRRK2 mutation is uncommon in an Asian cohort of Parkinson's disease patients

Comprehensive analysis of the LRRK2 gene in sixty families with Parkinson's disease

“…For example, the p.G2019S mutation seems rare in Asian populations. 22 The pathogenic role of the p.G2019S and p.R1441C mutations is well established on the basis of the absence in a large number of control chromosomes, cosegregation with disease, conservation and crucial structural position of the amino acids involved. 9,12 -14,16 -18 The p.G2019S mutation was identified previously by us and other groups in B3 -6% of samples with familial PD (autosomal dominant families, and sib-pairs) from several European and North American countries, and even in B1% of sporadic PD cases from the United Kingdom and Italy, while it was absent in more than 4000 control individuals.…”

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

“…The frequency of the most common mutation, G2019S, varies across populations, is most common in North African and Jewish populations [210,213], while it seems to be rare in Asian [214,215] and South African populations [216]. Studies that examined the origin of the mutation by haplotype analyses reported only three haplotypes, indicating founder effects [212].…”

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

“…Although three Japanese index patients with p.G2019S were reported, 21,22 we did not detect p.G2019S in our Japanese Ad-PD cohort, consistent with previous reports, showing that p.G2019S is rare in Asian cohorts. 10,11,18,23 Indeed, the substantial differences in allele frequencies of the synonymous LRRK2 polymorphisms (rs10878245, rs1427263, rs11176013, rs17466213 and rs3761863) highlight the genetic diversity between the Japanese and Caucasian Ad-PD patients (Table 2). These findings raise the possibility that mutational analysis focusing on previously identified mutation hotspots may underestimate the incidence of mutations; therefore, a comprehensive analysis of every coding exon is warranted.…”

“…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.…”