Submitted August 13, 2003
Accepted September 22, 2003
Unique CD18 mutations involving a deletion in the extracellular stalk region and a major truncation of the cytoplasmic domain in a patient with leukocyte adhesion deficiency type 1
Patricia Hixson, C Wayne Smith, Susan B Shurin, and Michael F Tosi*
Department of Pediatrics, Section of Leukocyte Biology, Baylor College of Medicine, Houston, TX, USA
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, USA
* Corresponding author; email: mtosi{at}bcm.tmc.edu.
Two novel CD18 mutations were identified in a patient who was a compound heterozygote with type 1 leukocyte adhesion deficiency and whose phenotype was typical except that he exhibited hypertrophic scarring. A deletion of 36 nucleotides in exon 12 (1622del36) predicted the net loss of 12 amino acid (a.a.) residues in the third cysteine-rich repeat of the extracellular stalk region (mut-1). A nonsense mutation in exon 15 (2200G
T), predicted a 36 a.a. truncation of the cytoplasmic domain (mut-2). LFA-1 and Mac-1 containing the mut-1 
2 subunit were expressed at very low levels compared to wild type (wt) 2. Mac-1 and LFA-1 expression with the mut-2 2 subunit were equivalent to results with wt 2. Binding function of Mac-1 with mut-2 2 was equivalent to that with wt 2. However, binding function of LFA-1 with the mut-2 2 subunit was reduced by 50% vs. wt 2. It was concluded that: (1) the portion of the CD18 stalk region deleted in mut-1 is critical for 2 integrin heterodimer expression, but the portion of the cytoplasmic domain truncated in mut-2 is not; (2) the mut-2 cytoplasmic domain truncation impairs binding function of LFA-1 but not of Mac-1. Studies with patient neutrophils (PMN) were consistent with functional impairment of LFA-1, but not of Mac-1.
