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.
The Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037-1000, USA. beutler@scripps.edu
Ernest
E
Beutler
Lisa
L
Beutler
Carol
C
West
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