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Blood, 1 March 2005, Vol. 105, No. 5, pp. 1881-1890. Prepublished online as a Blood First Edition Paper on September 9, 2004; DOI 10.1182/blood-2003-12-4420. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-12-4420v1 105/5/1881    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 Lee, W.-I Articles by Ochs, H. D. Search for Related Content PubMed PubMed Citation Articles by Lee, W.-I Articles by Ochs, H. D. Related Collections Signal Transduction Clinical Trials and Observations Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Molecular analysis of a large cohort of patients with the hyper immunoglobulin M (IgM) syndrome Wen-I Lee, Troy R. Torgerson, Michael J. Schumacher, Leman Yel, Qili Zhu, and Hans D. Ochs From the Department of Pediatrics, University of Washington, School of Medicine, Seattle; the Department of Pediatrics, Chang Gung Children's Hospital and Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan; the Department of Pediatrics and Medicine, University of Arizona, Tucson; and the Department of Medicine, University of California, Irvine. The hyper immunoglobulin M (IgM) syndrome (HIGM), characterized by recurrent infections, low serum IgG and IgA, normal or elevated IgM, and defective class switch recombination and somatic hypermutation, is a heterogenous disorder with at least 5 distinct molecular defects, including mutations of the genes coding for the CD40 ligand (CD40L) and IKK-gamma (NEMO) genes, both X-linked; and mutations of CD40, activation-induced cytidine deaminase (AICDA), and uracil-DNA glycosylase (UNG), associated with autosomal recessive HIGM syndromes. To investigate the molecular basis of HIGM, we determined the prevalence of mutations affecting these 5 genes in a cohort of 140 patients (130 males and 10 females). Those patients without a molecular diagnosis were subsequently evaluated for mutations of the following genes: inducible CO-stimulator molecule (ICOS), ICOS ligand (ICOSL), and if male, Bruton tyrosine kinase (Btk) and SLAM-associated protein (SAP/SH2D1A). We found mutations of CD40L in 98 males; AICDA in 4 patients (3 males, 1 female); UNG in one adult male; and Btk in 3 boys. Of the remaining 25 males, one infant with hypohidrotic ectodermal dysplasia had a mutation of NEMO. None of the remaining 33 patients (24 males/9 females) had mutations affecting CD40, ICOS, ICOSL, or SH2D1, and are best classified as common variable immune deficiency (CVID), although other genes, including some not yet identified, may be responsible. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Herve, I. Isnardi, Y.-s. Ng, J. B. Bussel, H. D. Ochs, C. Cunningham-Rundles, and E. Meffre CD40 ligand and MHC class II expression are essential for human peripheral B cell tolerance J. Exp. Med., July 9, 2007; 204(7): 1583 - 1593. [Abstract] [Full Text] [PDF] M. Erdos, K. Alapi, and L. Marodi Retrospective diagnosis of X-linked hyper-IgM syndrome in a family with multiple deaths of affected males Haematologica, February 1, 2007; 92(2): 281 - 282. [Abstract] [Full Text] [PDF] D. P. Huston Update in allergy and immunology. Ann Intern Med, September 19, 2006; 145(6): 454 - 458. [Full Text] [PDF] K. Warnatz, L. Bossaller, U. Salzer, A. Skrabl-Baumgartner, W. Schwinger, M. van der Burg, J. J. M. van Dongen, M. Orlowska-Volk, R. Knoth, A. Durandy, et al. Human ICOS deficiency abrogates the germinal center reaction and provides a monogenic model for common variable immunodeficiency Blood, April 15, 2006; 107(8): 3045 - 3052. [Abstract] [Full Text] [PDF]

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