LRRK2G2019S as a Cause of Parkinson's Disease in North African Arabs

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

“…In all families, the disease was similar to typical PD with relatively late onset, but there was a wide range of neuropathological findings. A large number of genetic variations have since then been discovered in different populations, not only in familial but also in apparently sporadic cases [209][210][211]. Relatively few of these variants are considered as established pathogenic mutations.…”

“…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].…”

Update on the Functional Biology of Lrrk2

“…Remarkably, it accounts for 29% of Ashkenazi Jews and 37% of North African Arabs with familial parkinsonism and for 13 and 30%, respectively, of patients with seemingly sporadic PD in these two populations [4,9,11]. Furthermore, the Lrrk2 G2385R and R1628P substitutions are risk factors for sporadic PD in Asian populations [12][13][14].…”

Parkinson's Disease: The LRRK2-G2019S mutation: opening a novel era in Parkinson's disease genetics

“…Two studies recently published in The New England Journal of Medicine report an astonishing high prevalence of a single mutation in leucine-rich repeat kinase 2 (LRRK2), G2019S, in North African Arabs and Ashkenazi Jews with PD. 1,2 Mutations in the LRRK2 gene were first identified in 2004 in families with autosomal-dominant PD; 3,4 soon thereafter, the G2019S mutation (c.G6055A) was identified by several groups as a common cause of this disease, being found not only in B5 -6% of familial PD but also in B1 -2% of sporadic PD in several European and US populations. 5 -9 In one of the novel studies, 2 22 out of 120 Ashkenazi Jewish patients with PD (18.3%, 95% confidence intervals (CI) 11.9 -26.4) and four of 317 controls (1.3%, CI 0.34 -3.2) carried the G2019S mutation.…”

“…A few carriers of the G2019S mutation also carry parkin gene mutations. 1,13 Digenic or polygenic inheritance could explain the lack of a Mendelian pattern of inheritance in most PD families. We do not currently understand the mechanisms underlying the large variability in onset age and other clinical features, observed even among the members of the same G2019S family; other factors must modify the expression and progression of the disease.…”