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Blood, 1 February 2004, Vol. 103, No. 3, pp. 1105-1113. Prepublished online as a Blood First Edition Paper on September 25, 2003; DOI 10.1182/blood-2003-08-2780. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-08-2780v1 103/3/1105    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hixson, P. Articles by Tosi, M. F. Search for Related Content PubMed PubMed Citation Articles by Hixson, P. Articles by Tosi, M. F. Related Collections Phagocytes Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES 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 From the Department of Pediatrics, Section of Leukocyte Biology, Baylor College of Medicine, Houston, TX; and Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH. 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 (aa) 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-aa truncation of the cytoplasmic domain (mut-2). Lymphocyte function-associated antigen 1 (LFA-1) and macrophage antigen-1 (Mac-1) containing the mut-1 2 subunit were expressed at very low levels compared with 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% versus 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; and (2) the mut-2 cytoplasmic domain truncation impairs binding function of LFA-1 but not of Mac-1. Studies with the patient's neutrophils (PMNs) were consistent with functional impairment of LFA-1 but not of Mac-1. (Blood. 2004;103:1105-1113) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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