Leukocytes from four patients with complete or partial Leu-CAM deficiency contain the common beta-subunit precursor and beta-subunit messenger RNA.
Deficiency of a family of three leukocyte adhesion molecules (Leu-CAM) is associated with recurrent and life-threatening bacterial infections in man. Each of the three antigens, Mo1, LFA-1, and Leu M5 has a distinct alpha subunit noncovalently associated with a common beta subunit that appears to be required for the expression of these antigens on the cell surface. To investigate the molecular basis of Leu-CAM deficiency, we studied leukocytes from four unrelated patients suffering from complete or partial Leu-CAM deficiency using immunoprecipitation of metabolically labeled proteins, RNA extraction, and Northern blot analysis. We found that B cells from all four patients synthesized a normal sized beta subunit precursor that either failed to "mature" or matured only partially to the membrane expressed form. B cells from all four patients also had a single normal sized beta subunit mRNA of approximately 3.4 kb. Leu-CAM deficiency, in these unrelated patients, is not due to the absence of the beta chain gene or to aberrant splicing of its mRNA and are consistent with a defective beta subunit gene resulting in abnormal posttranslational processing of the synthesized molecule.
D000954:Antigens, Surface / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism*; D018821:CD18 Antigens; D002472:Cell Transformation, Viral; D004247:DNA / Q000235:genetics; D004854:Herpesvirus 4, Human; D006801:Humans; D007163:Immunosorbent Techniques; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D009693:Nucleic Acid Hybridization; D011498:Protein Precursors / Q000096:biosynthesis*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics*; D014158:Transcription, Genetic
D000954:Antigens, Surface; D018821:CD18 Antigens; D008565:Membrane Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D004247:DNA