Genotype, phenotype, and outcomes of nine patients with T-B+NK+ SCID

Authors

  • Grace P. Yu,

    1. Division of Immunology and Allergy, Department of Pediatrics, Stanford University School of Medicine and Lucile Packard Children’s Hospital at Stanford, Palo Alto, CA
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    • Both authors contributed equally.

  • Kari C. Nadeau,

    1. Division of Immunology and Allergy, Department of Pediatrics, Stanford University School of Medicine and Lucile Packard Children’s Hospital at Stanford, Palo Alto, CA
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    • Both authors contributed equally.

  • David R. Berk,

    1. Departments of Medicine and Pediatrics, Division of Dermatology, Washington University School of Medicine, St. Louis, MO
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  • Geneviève de Saint Basile,

    1. Inserm, U768, Paris, France
    2. IRNEM (IFR95), Université Paris Descartes, Paris, France
    3. AP-HP, Hôpital Necker Enfants-Malades, Unité d’Immunologie-Hématologie Pédiatrique, Paris, France
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  • Nathalie Lambert,

    1. AP-HP, Hôpital Necker Enfants-Malades, Unité d’Immunologie-Hématologie Pédiatrique, Paris, France
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  • Perrine Knapnougel,

    1. Inserm, U768, Paris, France
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  • Joseph Roberts,

    1. Department of Pediatrics and Immunology, Duke University Medical Center, Durham, NC
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  • Kristina Kavanau,

    1. Division of Blood and Marrow Transplantation, Department of Pediatrics, University of California San Francisco Benioff Children’s Hospital, San Francisco, CA
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  • Elizabeth Dunn,

    1. Division of Blood and Marrow Transplantation, Department of Pediatrics, University of California San Francisco Benioff Children’s Hospital, San Francisco, CA
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  • E. Richard Stiehm,

    1. Division of Immunology, Allergy and Rheumatology, Department of Pediatrics, Mattel Children’s Hospital at the University of California Los Angeles, Los Angeles, CA
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  • David B. Lewis,

    1. Division of Immunology and Allergy, Department of Pediatrics, Stanford University School of Medicine and Lucile Packard Children’s Hospital at Stanford, Palo Alto, CA
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  • Dale T. Umetsu,

    1. Division of Allergy and Immunology, Department of Pediatrics, Children’s Hospital Boston, Boston, MA
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  • Jennifer M. Puck,

    1. Department of Pediatrics, Institute for Human Genetics, University of California San Francisco Benioff Children’s Hospital, San Francisco, CA, USA
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  • Morton J. Cowan

    1. Division of Blood and Marrow Transplantation, Department of Pediatrics, University of California San Francisco Benioff Children’s Hospital, San Francisco, CA
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Morton J. Cowan, MD, Chief, Division of Blood and Marrow Transplantation, University of California San Francisco Benioff Children’s Hospital, Room M659, 505 Parnassus Ave., San Francisco, CA 94143-1278, USA
Tel.: +1 415 476 2188
Fax: +1 415 502 4867
E-mail: mcowan@peds.ucsf.edu

Abstract

Yu GP, Nadeau KC, Berk DR, de Saint Basile G, Lambert N, Knapnougel P, Roberts J, Kavanau K, Dunn E, Stiehm ER, Lewis DB, Umetsu DT, Puck JM, Cowan MJ. Genotype, phenotype, and outcomes of nine patients with T-B+NK+ SCID.
Pediatr Transplantation 2011: 15: 733–741. © 2011 John Wiley & Sons A/S.

Abstract:  There are few reports of clinical presentation, genotype, and HCT outcomes for patients with T-B+NK+ SCID. Between 1981 and 2007, eight of 84 patients with SCID who received and/or were followed after HCT at UCSF had the T-B+NK+ phenotype. One additional patient with T-B+NK+ SCID was identified as the sibling of a patient treated at UCSF. Chart reviews were performed. Molecular analyses of IL7R, IL2RG, JAK3, and the genes encoding the CD3 T-cell receptor components δ (CD3D), ε (CD3E), and ζ (CD3Z) were carried out. IL7R mutations were documented in four patients and CD3D mutations in two others. Three patients had no defects found. Only two of nine patients had an HLA-matched related HCT donor. Both survived, and neither developed GVHD. Five of seven recipients of haploidentical grafts survived. Although the majority of reported cases of T-B+NK+ SCID are caused by defects in IL7R, CD3 complex defects were also found in this series and should be considered when evaluating patients with T-B+NK+ SCID. Additional genes, mutations in which account for T-B+NK+ SCID, remain to be found. Better approaches to early diagnosis and HCT treatment are needed for patients lacking an HLA-matched related donor.

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