title: A point mutation in the protein 4.2 gene (allele 4.2 Tozeur) associated with hereditary haemolytic anaemia.
abstract: A recessively transmitted haemolytic anaemia associated with the lack of protein 4.2 was found in a Tunisian kindred. Trace amounts of this protein (72 kD component) became visible using high-sensitivity Western blots. Band 3 and ankyrin genes were excluded as candidate genes by linkage studies, and nucleotide sequencing of band 3 cytoplasmic domain cDNA revealed no alteration. In contrast, protein 4.2 gene contained in the homozygous state a mutation at position 310: CGA-->CAA (Arg-->Gln). This mutation defining allele 4.2 Tozeur was co-inherited with the disease. The mRNA encoding the variant protein was normal in size and approximately normal in amount. Recombinant protein 4.2 Tozeur bound normally to red cell IOVs but disclosed an increased susceptibility to proteolysis in vitro. We infer that the nearly total absence of protein 4.2 in the patients results from imbalance between destruction and synthesis of mutated protein 4.2 prior to its binding to the membrane.
authors.affiliation: CNRS URA 1171, Institut Pasteur de Lyon, France.
authors.forename: S
authors.initials: S
authors.lastname: Hayette
authors.forename: L
authors.initials: L
authors.lastname: Morle
authors.forename: M
authors.initials: M
authors.lastname: Bozon
authors.forename: A
authors.initials: A
authors.lastname: Ghanem
authors.forename: M
authors.initials: M
authors.lastname: Risinger
authors.forename: C
authors.initials: C
authors.lastname: Korsgren
authors.forename: M J
authors.initials: MJ
authors.lastname: Tanner
authors.forename: S
authors.initials: S
authors.lastname: Fattoum
authors.forename: C M
authors.initials: CM
authors.lastname: Cohen
authors.forename: J
authors.initials: J
authors.lastname: Delaunay
mesh_terms: D000743:Anemia, Hemolytic / Q000235:genetics*; D001483:Base Sequence; D001798:Blood Proteins / Q000172:deficiency / Q000235:genetics*; D015152:Blotting, Northern; D015153:Blotting, Western; D003598:Cytoskeletal Proteins; D005260:Female; D006801:Humans; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011485:Protein Binding; D011994:Recombinant Proteins
chemical_list: D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; C044791:erythrocyte membrane band 4.2 protein