A point mutation associated with leukocyte adhesion deficiency type 1 of moderate severity

Leukocyte adhesion deficiency (LAD) is a genetic disease characterized clinically by severe bacterial infections, and biochemically by a deficiency in the surface expression of the CD11/CD18 leukocyte integrins. We studied a teenage girl with the moderate deficiency phenotype of LAD. B-lymphoblastoid cells from this patient displayed approximately 5% of normal levels of CD11/CD18 on the cell surface. Although a normal sized CD18 mRNA was detectable on Northern blotting, a small CD18 protein was present on Western blotting. Sequencing of the RNA revealed a single base pair substitution resulting in a glycine to serine amino acid substitution at amino acid 284. This amino acid substitution occurs within a highly conserved region of the extracellular domain of CD18 in which several other mutations have been identified in LAD.