Mutations in the gene encoding cytosolic β-glucosidase in Gaucher disease

Abstract

Patients with Gaucher disease have a deficiency of the lysosomal acid β-glucosidase. The phenotypes of genotypically identical patients with Gaucher disease may differ markedly. We have examined the possibility that polymorphisms in another β-glucosidase are responsible for this variability in the phenotype. Sequence analysis of the gene encoding cytosolic β-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.