Heterogeneous mutations in the β 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 αβ heterodimers containing identical 95,000 dalton β subunits. Here we demonstrate that the primary defect in LAD is in the β subunit gene. We identified five distinct β subunit phenotypes in LAD patients: undetectable β subunit mRNA and protein precursor; low levels of β subunit mRNA and precursor; an aberrantly large β subunit precursor, probably due to an extra glycosylation site; an aberrantly small precursor; and a grossly normal precursor. Mutant β subunit precursors from LAD patients failed to associate with the LFA-1 α subunit. In family studies, inheritance of the aberrant precursors correlates with the known inheritance of the LAD defect.