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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 (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 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 Social Bookmarking                   What's this? Submitted September 18, 2002 Accepted October 10, 2002 Insights into leukocyte adhesion deficiency type II from a novel mutation in the GDP-fucose transporter gene Andres Hidalgo, Songhui Ma, Anna J Peired, Linnea A Weiss, Charlotte Cunnigham-Rundles, and Paul S Frenette* Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA Division of Clinical Immunology, Mount Sinai School of Medicine, New York, NY, USA * Corresponding author; email: paul.frenette{at}mssm.edu. Leukocyte Adhesion Deficiency type II (LADII) is characterized by defective selectin ligand formation, recurrent infections and mental retardation. This rare syndrome has only been described in two kindreds of Middle Eastern descent which have differentially responded to exogenous fucose treatment. The molecular defect was recently ascribed to single and distinct missense mutations in a putative Golgi 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 fibroblasts derived from the patient did not rescue fucosylation, suggesting that the deletion ablated the activity of the transporter. Administration of oral L-fucose to the patient produced a molecular and clinical response 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 NOD/SCID mice. However, fucose supplementation induced an 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. D. Notarangelo and R. Badolato Leukocyte trafficking in primary immunodeficiencies J. Leukoc. Biol., March 1, 2009; 85(3): 335 - 343. [Abstract] [Full Text] [PDF] 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. 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