title: Three unique base pair changes in a family with Gaucher disease.
abstract: Single-stranded cDNA was prepared from RNA obtained from a patient with type 1 Gaucher disease. The cDNA was amplified in vitro and analyzed by sequencing. Three base-pair changes were identified which included a G to C transversion at nucleotide 3119 of the active gene (Asp140----His), an A to C transversion at nucleotide 3170 (Lys157----Gln) and a G to A change at nucleotide 5309 (Glu326----Lys). To study the mode of inheritance of the three different base-pair changes, genomic DNA was prepared from blood or skin fibroblasts of several family members. Genomic glucocerebrosidase DNA sequences were amplified and subjected to hybridization with allele-specific oligonucleotides (ASOs). The hybridization profiles demonstrated that two of the base-pair changes originated from the mother and were transmitted to her two affected sons and to a grandchild, while the third base-pair change, originating from the father, was transmitted to his two affected sons, a carrier daughter and a second grandchild. Tests of other patients with Gaucher disease failed to disclose the presence of the three base-changes. This is a unique family with three base-pair changes tightly linked to Gaucher disease.
authors.affiliation: Weizmann Institute of Science, Rehovot, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Eyal
authors.forename: N
authors.initials: N
authors.lastname: Firon
authors.forename: S
authors.initials: S
authors.lastname: Wilder
authors.forename: E H
authors.initials: EH
authors.lastname: Kolodny
authors.forename: M
authors.initials: M
authors.lastname: Horowitz
mesh_terms: D001482:Base Composition; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA; D005260:Female; D005776:Gaucher Disease / Q000201:enzymology / Q000235:genetics*; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction
chemical_list: D004247:DNA; D005962:Glucosylceramidase