The Journal of Allergy and Clinical Immunology
Volume 124, Issue 6 , Pages 1289-1302.e4 , December 2009

Large deletions and point mutations involving the dedicator of cytokinesis 8 (DOCK8) in the autosomal-recessive form of hyper-IgE syndrome

  • Karin R. Engelhardt, Dr

      Affiliations

    • Department of Immunology and Molecular Pathology, Royal Free Hospital and University College London, London, UK
    • These authors contributed equally to this work.
    • ,
  • Sean McGhee, MD

      Affiliations

    • Division of Immunology, Allergy and Rheumatology, Department of Pediatrics, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, Calif
    • These authors contributed equally to this work.
    • ,
  • Sabine Winkler, MSc

      Affiliations

    • Department of Immunology and Molecular Pathology, Royal Free Hospital and University College London, London, UK
    • ,
  • Atfa Sassi, PhD

      Affiliations

    • Laboratoire d'immunologie, vaccinologie et génétique moléculaire, Institut Pasteur de Tunis, Tunisia
    • ,
  • Cristina Woellner, MSc

      Affiliations

    • Department of Immunology and Molecular Pathology, Royal Free Hospital and University College London, London, UK
    • ,
  • Gabriela Lopez-Herrera, PhD

      Affiliations

    • Department of Immunology and Molecular Pathology, Royal Free Hospital and University College London, London, UK
    • ,
  • Andrew Chen

      Affiliations

    • Division of Immunology, Allergy and Rheumatology, Department of Pediatrics, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, Calif
    • ,
  • Hong Sook Kim, PhD

      Affiliations

    • Division of Immunology, Allergy and Rheumatology, Department of Pediatrics, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, Calif
    • ,
  • Maria Garcia Lloret, MD

      Affiliations

    • Division of Immunology, Allergy and Rheumatology, Department of Pediatrics, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, Calif
    • ,
  • Ilka Schulze, MD

      Affiliations

    • Center of Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany
    • ,
  • Stephan Ehl, MD

      Affiliations

    • Center of Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany
    • ,
  • Jens Thiel, MD

      Affiliations

    • Center of Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany
    • ,
  • Dietmar Pfeifer, Dr

      Affiliations

    • Department of Hematology/Oncology, University Medical Center Freiburg, Freiburg, Germany
    • ,
  • Hendrik Veelken, MD

      Affiliations

    • Department of Hematology/Oncology, University Medical Center Freiburg, Freiburg, Germany
    • ,
  • Tim Niehues, MD

      Affiliations

    • HELIOS Klinikum Krefeld, Zentrum für Kinder-und Jugendmedizin, Krefeld, Germany
    • ,
  • Kathrin Siepermann, MD

      Affiliations

    • HELIOS Klinikum Krefeld, Zentrum für Kinder-und Jugendmedizin, Krefeld, Germany
    • ,
  • Sebastian Weinspach, MD

      Affiliations

    • Department of Pediatric Oncology, Hematology and Clinical Immunology, Center of Child and Adolescent Medicine, Heinrich-Heine-University Dusseldorf, Duesseldorf, Germany
    • ,
  • Ismail Reisli, MD

      Affiliations

    • Selcuk University, Division of Pediatric Allergy and Immunology, Konya, Turkey
    • ,
  • Sevgi Keles, MD

      Affiliations

    • Selcuk University, Division of Pediatric Allergy and Immunology, Konya, Turkey
    • ,
  • Ferah Genel, MD

      Affiliations

    • Behcet Uz State Hospital Division of Pediatric Immunology, Izmir, Turkey
    • ,
  • Necil Kutuculer, MD

      Affiliations

    • Ege University Faculty of Medicine, Department of Pediatrics, Izmir, Turkey
    • ,
  • Yıldız Camcıoğlu, MD

      Affiliations

    • Division of Pediatric Allergy-Immunology and Infectious Diseases, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
    • ,
  • Ayper Somer, MD

      Affiliations

    • Division of Infectious Diseases and Immunology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
    • ,
  • Elif Karakoc-Aydiner, MD

      Affiliations

    • Division of Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey
    • ,
  • Isil Barlan, MD

      Affiliations

    • Division of Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey
    • ,
  • Andrew Gennery, MD

      Affiliations

    • Institute of Cellular Medicine, Child Health, University of Newcastle Upon Tyne, Newcastle upon Tyne, UK
    • ,
  • Ayse Metin, MD, PhD

      Affiliations

    • Pediatric Immunology Unit, SB Ankara Diskapi Children's Hospital, Ankara, Turkey
    • ,
  • Aydan Degerliyurt, MD

      Affiliations

    • Pediatric Immunology Unit, SB Ankara Diskapi Children's Hospital, Ankara, Turkey
    • ,
  • Maria C. Pietrogrande, MD

      Affiliations

    • Department of Maternal and Pediatric Sciences, University of Milan, Fondazione IRCCS Policlinico Milano, Milan, Italy
    • ,
  • Mehdi Yeganeh, MD

      Affiliations

    • Immunology Asthma and Allergy Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
    • ,
  • Zeina Baz, MD

      Affiliations

    • Department of Pediatrics, St George Hospital University Medical Center, Beirut, Lebanon
    • ,
  • Salem Al-Tamemi, MD

      Affiliations

    • Department of Pediatrics, Sultan Qaboos University, Muscat, Oman
    • ,
  • Christoph Klein, MD, PhD

      Affiliations

    • Department of Pediatric Hematology/Oncology, Hannover Biomedical Research School, Hannover, Germany
    • ,
  • Jennifer M. Puck, MD

      Affiliations

    • University of California, San Francisco, Calif
    • ,
  • Steven M. Holland, MD

      Affiliations

    • Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Md
    • ,
  • Edward R.B. McCabe, MD, PhD

      Affiliations

    • Departments of Pediatrics, Human Genetics, and Bioengineering, and the Center for Society and Genetics, UCLA, Los Angeles, Calif
    • ,
  • Bodo Grimbacher, MD

      Affiliations

    • Department of Immunology and Molecular Pathology, Royal Free Hospital and University College London, London, UK
    • These authors contributed equally to this work.
    • Corresponding Author InformationReprint requests: Bodo Grimbacher, MD, Department of Immunology and Molecular Pathology, Royal Free Hospital and University College London, Pond Street, London NW3 2QG, United Kingdom.
    • ,
  • Talal A. Chatila, MD, MSc

      Affiliations

    • Division of Immunology, Allergy and Rheumatology, Department of Pediatrics, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, Calif
    • These authors contributed equally to this work.
    • Corresponding Author InformationTalal Chatila, MD, MSc, Division of Pediatric, Immunology, Allergy and Rheumatology, MDCC 12-430, Mail Code 175217, David Geffen School of Medicine, University of California at Los Angeles, 10833 Le Conte Avenue Los Angeles, CA 90095-1752.

Received 23 September 2009 ,Revised 22 October 2009 ,Accepted 26 October 2009.

References 

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  2. Grimbacher B, Holland SM, Puck JM. Hyper-IgE syndromes. Immunol Rev. 2005;203:244–250
  3. Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, et al. STAT3 mutations in the hyper-IgE syndrome. N Engl J Med. 2007;357:1608–1619
  4. Grimbacher B, Schaffer AA, Holland SM, Davis J, Gallin JI, Malech HL, et al. Genetic linkage of hyper-IgE syndrome to chromosome 4. Am J Hum Genet. 1999;65:735–744
  5. Woellner C, Gertz EM, Schäffer AA, Lagos M, Perro M, Glocker EO, et al. Mutations in the signal transducer and activator of transcription 3 (STAT3) and diagnostic guidelines for the Hyper-IgE syndrome. J Allergy Clin Immunol. 2009;in press
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  8. Woellner C, Schaffer A, Puck JM, Renner ED, Knebel C, Holland SM, et al. The hyper IgE syndrome and mutations in TYK2. Immunity. 2007;26:535
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  11. Zhang Q, Davis JC, Lamborn IT, Freeman AF, Jing H, Favreau AJ, et al. Combined immunodeficiency associated with DOCK8 mutations. N Engl J Med. 2009 Sep 23;[Epub ahead of print]
  12. Al Khatib S, Keles S, Garcia-Lloret M, Karakoc-Aydiner E, Reisli I, Artac H, et al. Defects along the T(H)17 differentiation pathway underlie genetically distinct forms of the hyper IgE syndrome. J Allergy Clin Immunol. 2009;124:342–348
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  17. Miyamoto Y, Yamauchi J, Sanbe A, Tanoue A. Dock6, a Dock-C subfamily guanine nucleotide exchanger, has the dual specificity for Rac1 and Cdc42 and regulates neurite outgrowth. Exp Cell Res. 2007;313:791–804
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 Supported by National Institutes of Health grants 5R01AI065617 and 1R21AI087627 to T.C. and by the EU Marie-Curie grant MEXT-CT-2006-042316 and the European Community's 7th Framework Programme FP7/2007-2013 grant EURO-PADnet HEALTH-F2-2008-201549 to B.G.

 Disclosure of potential conflict of interest: K. R. Engelhardt, S. Winkler, and G. Lopez-Herrera are employed on a research grant from the European Union (EU Marie-Curie grant). S. McGhee is a board member of Madison's Foundation. E. R. B. McCabe has received research support from the National Institutes of Health/National Human Genome Research Institute. B. Grimbacher (EU Marie-Curie grant) has received research support from the European Union and the Primary Immunodeficiency Association. The rest of the authors have declared that they have no conflict of interest.

PII: S0091-6749(09)01604-2

doi: 10.1016/j.jaci.2009.10.038

The Journal of Allergy and Clinical Immunology
Volume 124, Issue 6 , Pages 1289-1302.e4 , December 2009

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