Mutations in the gene encoding cytosolic beta-glucosidase in Gaucher disease.
Patients with Gaucher disease have a deficiency of the lysosomal acid beta-glucosidase. The phenotypes of genotypically identical patients with Gaucher disease may differ markedly. We have examined the possibility that polymorphisms in another beta-glucosidase are responsible for this variability in the phenotype. Sequence analysis of the gene encoding cytosolic beta-glucosidase (GBA3) from 4 chromosomes revealed the presence of 4 single-nucleotide substitutions: c.316 G -->A (D106N), c.1353A-->G (Y451Y), c.1368T-->A (Y456X), and c.1540 to 1541AG -->T in the 3' untranslated region. We examined the DNA from 62 patients with Gaucher disease who were homozygous for the 1226A-->G (N370S) mutation and from 542 control subjects from various populations for these polymorphisms. Six of the possible 16 haplotypes were found, and none was over- or underrepresented among patients with the severe Gaucher disease phenotypes compared with those from patients with mild phenotypes.
Beutler
Ernest
E
The Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037-1000, USA. beutler@scripps.edu
Beutler
Lisa
L
West
Carol
C
D001483:Base Sequence; D004247:DNA / Q000097:blood / Q000235:genetics; D017931:DNA Primers; D005776:Gaucher Disease / Q000201:enzymology / Q000235:genetics*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D001617:beta-Glucosidase / Q000235:genetics*
D017931:DNA Primers; D004247:DNA; D001617:beta-Glucosidase