title: A novel point mutation in CD18 causing the expression of dysfunctional CD11/CD18 leucocyte integrins in a patient with leucocyte adhesion deficiency (LAD).
abstract: Leucocyte adhesion deficiency type 1 (LAD-1) is characterized by the incapacity of leucocytes to carry out their adhesion functions via their CD11/CD18 antigens, which are also referred to as the leucocyte integrins. The patients generally suffer from poor wound healing and recurrent bacterial and fungal infections. In severe cases, the infections are often systemic and life-threatening. A LAD patient (AW) of moderate phenotype has been identified but, unlike most other cases, the level of CD11/CD18 antigens on her leucocytes are uncharacteristically high for a LAD patient. Molecular analysis revealed that she is a compound heterozygote for CD18 mutations. She has inherited a D231H mutation from her father and a G284S mutation from her mother. By transfection studies, it was established that the G284S mutation does not support CD11/CD18 antigen expression on the cell surface. In contrast, the D231H mutation does not affect CD18 forming integrin heterodimers with the CD11 antigens on the cell surface. However, the expressed integrins with the D231H mutation are not adhesive to ligands.
authors.affiliation: The MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, Oxford, UK.
authors.forename: E C
authors.initials: EC
authors.lastname: Mathew
authors.forename: J M
authors.initials: JM
authors.lastname: Shaw
authors.forename: F A
authors.initials: FA
authors.lastname: Bonilla
authors.forename: S K
authors.initials: SK
authors.lastname: Law
authors.forename: D A
authors.initials: DA
authors.lastname: Wright
mesh_terms: D000818:Animals; D018845:CD11 Antigens / Q000235:genetics* / Q000276:immunology; D018821:CD18 Antigens / Q000235:genetics* / Q000276:immunology; D019556:COS Cells; D002675:Child, Preschool; D005260:Female; D006801:Humans; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000235:genetics* / Q000276:immunology; D008297:Male; D017354:Point Mutation
chemical_list: D018845:CD11 Antigens; D018821:CD18 Antigens