BACKGROUND: Gaucher disease (GD) is a heterogeneous disease characterized by an 
impaired activity of the lysosomal glucocerebrosidase. This heterogeneity is 
attributed in part to the existence of a large number of mutations in the 
corresponding gene.
SUBJECTS AND METHODS: To establish genotype-phenotype relationships, we analyzed 
the residual enzyme activities of six naturally occurring mutations found in 
Spanish population in the glucocerebrosidase gene [c.160G > A (V15M), c.485T>C 
(M123T), c.914C>T (P266L), c.1124T>C (L336P), c.1207A>C (S364R) and 
c.1510-1512delTCT (S465del)]. The mutated genes were subcloned into the 
mammalian expression vector pCR 3.1 and expressed by transient transfection in 
COS cells. The enzymatic activity of the expressed protein were measured and 
compared with the wild-type human glucocerebrosidase cDNA. Also, two previously 
alleles, c.1226A>G (N370S) and c.1448T>C (L444P), were used for comparative 
purposes.
RESULTS: The residual activity of the expressed proteins using the synthetic 
substrate (4-methylumbelliferyl-beta-D-glucopyranoside, 4MU-Glu) ranged from 
5.5% (for the 3-bp deletion) to 42.7% (for S364R mutation) of the activity of 
the wild-type enzyme.
CONCLUSION: The present analyses may help to better understand the molecular 
basis and the pathogenesis of Gaucher disease. However, results of expression of 
mutated enzymes are necessary but not sufficient to explain the ultimate 
clinical outcome of Gaucher disease.