title: A 5' splice junction mutation leading to exon deletion in an Ashkenazic Jewish family with phosphofructokinase deficiency (Tarui disease).
abstract: A deficiency of the muscle isoform of the enzyme, phosphofructokinase (PFK, EC 2.7.1.11), leads to an illness (glycogenosis, Type VII) characterized by myopathy and hemolysis. A patient with this disease and an affected sister were found to have a G to A substitution at the 5' donor site of intron 5 of the PFK-M gene. This mutation led to a splicing defect: a complete deletion of the preceding exon in the patient's mRNA. The patient, an affected sister, and related and unrelated family members, who were of Ashkenazic Jewish background, were screened for the mutation by denaturing gradient gel electrophoresis and by allele specific hybridization of genomic DNA. The affected sisters are homozygous for the mutation, and their children, who are unaffected, are heterozygous. The only previously characterized genetic defect in this disease, found in a Japanese patient, was a G to T mutation at the beginning of intron 15 with splicing to a cryptic site within exon 15 (1). Both mutations lead to inframe deletions, but of different parts of the protein. The differences between the two aberrant proteins may account for clinical differences between our patients and the Japanese patient.
authors.affiliation: Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: N
authors.initials: N
authors.lastname: Raben
authors.forename: J
authors.initials: J
authors.lastname: Sherman
authors.forename: F
authors.initials: F
authors.lastname: Miller
authors.forename: H
authors.initials: H
authors.lastname: Mena
authors.forename: P
authors.initials: P
authors.lastname: Plotz
mesh_terms: D001483:Base Sequence; D002461:Cell Line, Transformed; D004247:DNA; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006014:Glycogen Storage Disease Type VII / Q000235:genetics*; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010732:Phosphofructokinase-1 / Q000172:deficiency / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017384:Sequence Deletion
chemical_list: D012333:RNA, Messenger; D004247:DNA; D010732:Phosphofructokinase-1