ABSTRACT
Gaucher disease (GD), the most frequent lysosomal storage disease, is caused by heterogeneous mutations in the locus coding for glucocerebrosidase (GBA). It is an autosomal recessive disorder with different phenotypes of which the most frequent is the nonneuronopathic or type 1, prevalent worldwide. To date, more than 430 mutations have been described, but their frequency distribution varies in different populations with four, N370S, L444P, IVS2 + 1G > A and 84insG, being the most frequent ones. In Venezuela, 20 unrelated index cases with GD type I were assessed for GBA mutation detection and for their in-phase haplotype identification, to gather genetic epidemiological data on the disease in the country and of its eventual ethnic origin. Ten missense mutations and two complex alleles were identified. The most frequent were N370S (42.5%), L444P (20%), IVS2+1G > A (10%) and R48W (5%); mutations R120W, P245H, H311R, R496H, W36X and R433G which were carried by a single chromosome each one. Three geographical foci were identified, displaying mutation heterogeneity. N370S had multiple genetic origins, different from the Ashkenazi's; a single common remote ancestor for this mutation in the country was dismissed, according to the haplotype analysis. All mutations have a likely European Caucasoid descent.
