Heterogeneous mutations in the beta subunit common to the LFA-1, Mac-1, and p150,95 glycoproteins cause leukocyte adhesion deficiency.
Leukocyte adhesion deficiency (LAD) is a heritable disease involving deficient expression of three related leukocyte adhesion glycoproteins: LFA-1, Mac-1, and p150,95. These proteins are alpha beta heterodimers containing identical 95,000 dalton beta subunits. Here we demonstrate that the primary defect in LAD is in the beta subunit gene. We identified five distinct beta subunit phenotypes in LAD patients: undetectable beta subunit mRNA and protein precursor; low levels of beta subunit mRNA and precursor; an aberrantly large beta subunit precursor, probably due to an extra glycosylation site; an aberrantly small precursor; and a grossly normal precursor. Mutant beta subunit precursors from LAD patients failed to associate with the LFA-1 alpha subunit. In family studies, inheritance of the aberrant precursors correlates with the known inheritance of the LAD defect.
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000954:Antigens, Surface / Q000235:genetics*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D002460:Cell Line; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000502:physiology*; D046911:Macromolecular Substances; D008970:Molecular Weight; D009154:Mutation; D010641:Phenotype
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D046911:Macromolecular Substances