Abstract
Mutations in the glucocerebrosidase (GBA) gene cause Gaucher disease (GD). The aim of this study was to characterise the GBA mutations and analyze genotype/phenotype relationships in 193 unrelated patients from the Spanish GD Registry. We have identified 98.7% of the mutated GBA alleles, finding 56 different GBA mutations and 66 genotypes causing GD in Spain: 47 previously described mutations and 9 novel mutations (4 missense R395C, R463H, W312R and V398I, 1 nonsense R359X, 4 frameshift c.708delC, c.1214-1215delGC, c.1439-1445del7 and c.42-65del24). The most prevalent mutations were N370S and L444P, accounting for 68.7% of the mutated alleles. A wide phenotypic difference was observed within each genotypic group, and 9% of diagnosed type 1 patients developed neurological involvement including parkisonism, tremor, hypoacusia and eye movements. All of these findings indicate that there is a significant genotypic heterogeneity that explains the huge phenotypic variation among Spanish GD patients.
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This study was supported by grants from FIS (G03/054, 03/0529, 04/2476, 05/0695, and 06/1253).
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Alfonso, P., Aznarez, S., Giralt, M. et al. Mutation analysis and genotype/phenotype relationships of Gaucher disease patients in Spain. J Hum Genet 52, 391–396 (2007). https://doi.org/10.1007/s10038-007-0135-4
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DOI: https://doi.org/10.1007/s10038-007-0135-4
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