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Current Pediatrics Reports

, Volume 3, Issue 1, pp 22–33 | Cite as

The Genetic and Molecular Basis of Severe Combined Immunodeficiency

  • Capucine PicardEmail author
  • Despina Moshous
  • Alain Fischer
Immunology (HB Gaspar, Section Editor)
  • 187 Downloads
Part of the following topical collections:
  1. Immunology

Abstract

Severe combined immunodeficiency (SCID) is a life-threatening disease caused by a heterogeneous group of genetic defects. It is characterized by profound defects of T-cell development, also affecting B and NK cells in some cases. Since the first molecular identification of a causal gene for SCID in 1985, 14 more molecular causes have been identified in patients with a classical SCID phenotype, with no T cells. Some genetic defects specifically block lymphocyte ontogeny, whereas others affect T-cell function and a few cause extra-hematopoietic alterations with a rare complex phenotype. Over the last 15 years, several new causal genes have been identified in patients with low T-cell counts and impaired T-cell function. Patients with a clinical SCID phenotype with normal numbers of dysfunctional T cells have also recently been reported. This last condition is described immunologically as combined immunodeficiency. These discoveries have expanded the complexity and difficulties of molecular characterization in patients with a clinical SCID phenotype. Studies of these disorders have increased our understanding of the role of single-gene products in the development, differentiation, and function of the immune system in humans.

Keywords

Severe combined immunodeficiency Primary immunodeficiencies T-cell lymphopenia Genetic defect 

Notes

Acknowledgments

We would like to thank all the members of our laboratory and unit for helpful discussions, and critical reading of the text, and our collaborators worldwide for their trust and patience.

Disclosure

Capucine Picard, Despina Moshous, and Alain Fischer declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer Science + Business Media New York 2014

Authors and Affiliations

  • Capucine Picard
    • 1
    • 2
    • 3
    Email author
  • Despina Moshous
    • 3
    • 4
    • 5
  • Alain Fischer
    • 3
    • 4
    • 5
    • 6
  1. 1.Study Center for Primary ImmunodeficienciesNecker-Enfant Malades Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP)ParisFrance
  2. 2.Laboratory of Human Genetics of Infectious Diseases, Necker BranchINSERM UMR 1163ParisFrance
  3. 3.Sorbonne Paris Cité, Imagine InstitutParis Descartes UniversityParisFrance
  4. 4.INSERM UMR 1163ParisFrance
  5. 5.Pediatric Hematology-Immunology UnitNecker Enfant Malades Hospital, AP-HPParisFrance
  6. 6.College de FranceParisFrance

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