MOLECULAR-CLONING AND CHARACTERIZATION OF DECAY-ACCELERATING FACTOR DEFICIENCY IN CROMER BLOOD-GROUP INAB PHENOTYPE

An additional decay-accelerating factor (DAF) mutation, designated as Inab phenotype in the Cromer blood group system, was recently identifi ed in a 28-year-old Japanese woman (H.A.). The red blood cells of H.A. , like those of other Inab phenotype individuals, were negative for Cr omer system antigens, Cr-a, Tc-a, Dr(a), UMC, and IFC. The deficiency of DAF on the red blood cells of H.A. has been shown by immunoblotting with a murine monoclonal antibody to DAF. Molecular analysis has show n that H.A. is homozygous for a single nucleotide substitution, C-1579 -->A, at the position 24 bp upstream of the 3'-end of exon 2 of the DA F gene. This substitution causes the activation of a novel cryptic spl ice site and results in the production of mRNA with a 26 bp deletion. The deletion introduces a reading frame shift and creates a stop codon immediately downstream of the deletion. Translation of mRNA would be terminated at the first amino acid residue of the second short consens us repeat (SCR2) domain (exon 3) of DAF. The functional domains of DAF 's complement regulatory activity and the carboxyterminal signal domai ns for glycosylphosphatidylinositol (GPI) anchoring are predicted to b e lacking in H.A. Thus, there would be no DAF present an the cell surf ace. (C) 1998 by The American Society of Hematology.