Glucocerebrosidase mutations are not a common risk factor for Parkinson disease in North Africa.
Mutations in the glucocerebrosidase gene (GBA) have recently been associated with an increased risk of Parkinson disease (PD). GBA mutations have been observed to be particularly prevalent in the Ashkenazi Jewish population. Interestingly, this population also has a high incidence of the Lrrk2 p.G2019S mutation which is similar in North African Arab-Berber populations. Herein, our sequencing of the GBA gene, in 33 North African Arab-Berber familial parkinsonism probands, identified two novel mutations in three individuals (p.K-26R and p.K186R). Segregation analysis of these two variants did not support a pathogenic role. Genotyping of p.K-26R, p.K186R and the common p.N370S in an ethnically matched series consisting of 395 patients with PD and 372 control subjects did not show a statistically significant association (P>0.05). The p.N370S mutation was only identified in 1 sporadic patient with PD and 3 control subjects indicating that the frequency of this mutation in the North African Arab-Berber population is much lower than that observed in Ashkenazi Jews, and therefore arose in the latter after expansion of the Lrrk2 p.G2019S variant in North Africa.
Nishioka
Kenya
K
Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Vilariño-Güell
Carles
C
Cobb
Stephanie A
SA
Kachergus
Jennifer M
JM
Ross
Owen A
OA
Wider
Christian
C
Gibson
Rachel A
RA
Hentati
Faycal
F
Farrer
Matthew J
MJ
D018912:Arabs; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D012307:Risk Factors; D014416:Tunisia
D005962:Glucosylceramidase