title: Gaucher disease type 1: cloning and characterization of a cDNA encoding acid beta-glucosidase from an Ashkenazi Jewish patient.
abstract: Gaucher disease (GD) type 1 is the most prevalent lysosomal storage disease and the most prevalent genetic disease among the Ashkenazi Jews. The defective activity of acid beta-glucosidase is the enzymatic basis of GD and is inherited as an autosomal recessive trait. To investigate the genetic basis of Ashkenazi Jewish GD type 1, a cDNA encoding acid beta-glucosidase was isolated from a cDNA library constructed using splenic poly(A)+RNA from a patient. The cDNA was sequenced to identify mutations, and the presence of a single missense mutation in the patients' genome was confirmed by selective oligonucleotide hybridization and by restriction endonuclease digestion analyses of amplified genomic sequences. This G----A transition (Arg-119 to Gln-119) was present heterozygously in the index patient and his affected third cousin but was not present in normal non-Jewish individuals. This mutation is the second single base mutation found in Ashkenazi Jewish GD type 1 patients. Furthermore, results obtained with the affected third cousin suggest that at least three mutant alleles may be present in this GD subpopulation.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029.
authors.forename: P N
authors.initials: PN
authors.lastname: Graves
authors.forename: G A
authors.initials: GA
authors.lastname: Grabowski
authors.forename: R
authors.initials: R
authors.lastname: Eisner
authors.forename: P
authors.initials: P
authors.lastname: Palese
authors.forename: F I
authors.initials: FI
authors.lastname: Smith
mesh_terms: D002648:Child; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis*; D005776:Gaucher Disease / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D005959:Glucosidases / Q000235:genetics*; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D009693:Nucleic Acid Hybridization
chemical_list: D004247:DNA; D005959:Glucosidases