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A point mutation in the protein 4.2 gene (allele 4.2 Tozeur) associated with hereditary haemolytic anaemia
Author(s) -
Hayette S.,
Morle L.,
Bozon M.,
Ghanem A.,
Risinger M.,
Korsgren C.,
Tanner M. J. A.,
Fattoum S.,
Cohen C. M.,
Delaunay J.
Publication year - 1995
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1995.tb08413.x
Subject(s) - point mutation , biology , ankyrin , gene , microbiology and biotechnology , mutation , genetics , snap23 , allele , complementary dna , ankyrin repeat , hspa2 , peptide sequence
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.