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Mutations in the glucocerebrosidase gene confer a risk for Parkinson disease in North Africa

Heterozygous mutations in the glucocerebrosidase gene ( GBA ) encoding the enzyme deficient in Gaucher disease (GD), an autosomal recessive lysosomal storage disease, are the most common risk factors for parkinsonism in several populations. A large meta-analysis, pooling genotyping data for the most common mutations from 16 different centers in the United States, Europe, Israel, and Asia, yielded a combined odds ratio (OR) for GBA mutations in subjects with Parkinson disease (PD) of >51 but did not include North Africans. Ashkenazi Jewish patients with PD had the highest mutation frequency (∼20%) (controls, 3%). The common LRRK2 G2019S mutation was also very frequent in Ashkenazi Jews (familial, 28%; isolated, 10%).2 This mutation, on the same haplotype,3 was also frequent in North African patients with PD (familial, 36%; isolated, 39%), who might, therefore, also have a high frequency of GBA mutations,2 although GBA mutations were not a risk factor for PD in Tunisian Berber Arabs.4

### Methods.

We studied 194 unrelated patients with PD as reported previously5 and 177 ethnically matched control subjects, all of North African ancestry. Most patients were from Algeria (n = 147), Morocco (n = 23), Tunisia (n = 14), and Libya (n = 1), and 9 were of unknown origin. Mean ± SD age at onset was 50.9 ± 12.9 years (range 12–78 years), mean age at examination was 58.8 ± 13.3 years (range 14–83 years), mean disease duration was 7.5 ± 5.9 years (range 0–35 years), 52% …