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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-09-2840. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-09-2840v1 101/5/1705    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hidalgo, A. Articles by Frenette, P. S. Search for Related Content PubMed PubMed Citation Articles by Hidalgo, A. Articles by Frenette, P. S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Phagocytes Cell Adhesion and Motility Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 March 2003, Vol. 101, No. 5, pp. 1705-1712 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Insights into leukocyte adhesion deficiency type 2 from a novel mutation in the GDP-fucose transporter gene Andrés Hidalgo, Songhui Ma, Anna J. Peired, Linnea A. Weiss, Charlotte Cunningham-Rundles, and Paul S. Frenette From the Divisions of Hematology and Clinical Immunology, Department of Medicine, Mount Sinai School of Medicine, New York, NY. Leukocyte adhesion deficiency type 2 (LADII) is characterized by defective selectin ligand formation, recurrent infection, and mental retardation. This rare syndrome has only been described in 2 kindreds of Middle Eastern descent who have differentially responded to exogenous fucose treatment. The molecular defect was recently ascribed to single and distinct missense mutations in a putative Golgi guanosine diphosphate (GDP)-fucose transporter. Here, we describe a patient of Brazilian origin with features of LADII. Sequencing of the GDP-fucose transporter revealed a novel single nucleotide deletion producing a shift in the open-reading frame and severe truncation of the polypeptide. Overexpression of the mutant protein in the patient's fibroblasts did not rescue fucosylation, suggesting that the deletion ablated the activity of the transporter. Administration of oral L-fucose to the patient produced molecular and clinical responses, as measured by the appearance of selectin ligands, normalization of neutrophil counts, and prevention of infectious recurrence. The lower neutrophil counts paralleled improved neutrophil interactions with activated endothelium in cremasteric venules of nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. However, fucose supplementation induced autoimmune neutropenia and the appearance of H antigen on erythrocytes, albeit without evidence of intravascular hemolysis. The robust response to fucose despite a severely truncated transporter suggests alternative means to transport GDP-fucose into the Golgi complex. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Yakubenia, D. Frommhold, D. Scholch, C. C. Hellbusch, C. Korner, B. Petri, C. Jones, U. Ipe, M. G. Bixel, R. Krempien, et al. Leukocyte trafficking in a mouse model for leukocyte adhesion deficiency II/congenital disorder of glycosylation IIc Blood, August 15, 2008; 112(4): 1472 - 1481. [Abstract] [Full Text] [PDF] C. C. Hellbusch, M. Sperandio, D. Frommhold, S. Yakubenia, M. K. Wild, D. Popovici, D. Vestweber, H.-J. Grone, K. von Figura, T. Lubke, et al. Golgi GDP-fucose Transporter-deficient Mice Mimic Congenital Disorder of Glycosylation IIc/Leukocyte Adhesion Deficiency II J. Biol. Chem., April 6, 2007; 282(14): 10762 - 10772. [Abstract] [Full Text] [PDF] B. Ma, J. L. Simala-Grant, and D. E. Taylor Fucosylation in prokaryotes and eukaryotes Glycobiology, December 1, 2006; 16(12): 158R - 184R. [Abstract] [Full Text] [PDF] Y. Helmus, J. Denecke, S. Yakubenia, P. Robinson, K. Luhn, D. L. Watson, P. J. McGrogan, D. Vestweber, T. Marquardt, and M. K. Wild Leukocyte adhesion deficiency II patients with a dual defect of the GDP-fucose transporter Blood, May 15, 2006; 107(10): 3959 - 3966. [Abstract] [Full Text] [PDF] H. O. Ishikawa, S. Higashi, T. Ayukawa, T. Sasamura, M. Kitagawa, K. Harigaya, K. Aoki, N. Ishida, Y. Sanai, and K. Matsuno Notch deficiency implicated in the pathogenesis of congenital disorder of glycosylation IIc PNAS, December 20, 2005; 102(51): 18532 - 18537. [Abstract] [Full Text] [PDF] Y. Katayama, A. Hidalgo, J. Chang, A. Peired, and P. S. Frenette CD44 is a physiological E-selectin ligand on neutrophils J. Exp. Med., April 18, 2005; 201(8): 1183 - 1189. [Abstract] [Full Text] [PDF] A. Hidalgo and P. S. Frenette Enforced fucosylation of neonatal CD34+ cells generates selectin ligands that enhance the initial interactions with microvessels but not homing to bone marrow Blood, January 15, 2005; 105(2): 567 - 575. [Abstract] [Full Text] [PDF] L. Huopaniemi, M. Kolmer, J. Niittymaki, M. Pelto-Huikko, and R. Renkonen Inflammation-induced transcriptional regulation of Golgi transporters required for the synthesis of sulfo sLex glycan epitopes Glycobiology, December 1, 2004; 14(12): 1285 - 1294. [Abstract] [Full Text] [PDF] T. Andrews and K. E. Sullivan Infections in Patients with Inherited Defects in Phagocytic Function Clin. Microbiol. Rev., October 1, 2003; 16(4): 597 - 621. [Abstract] [Full Text] [PDF]

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