Severe Combined Immune Deficiency (SCID): Genetics
Published Online: 15 NOV 2011
Copyright © 2001 John Wiley & Sons, Ltd. All rights reserved.
How to Cite
Fischer, A. 2011. Severe Combined Immune Deficiency (SCID): Genetics. eLS. .
- Published Online: 15 NOV 2011
Severe combined immunodeficiency consists of an array of genetically determined blocks in T-lymphocyte development. Characterisation of genetic defects contributes to a better understanding of lymphocyte differentiation pathways. Seventeen distinct defects have now been characterised that affect multiple steps of T lymphocytes ontogenesis, from defective survival of several haematopoietic lineage precursors, premature cell death of lymphocyte precursors, defective interleukin-7-dependent survival/proliferation of T-lymphocyte precursors, defective recombination of T-cell receptor (TCR) genes, defective (pre) TCR signalling and defective egress of the thymus. These disorders are life threatening because of the early onset of various infections notably caused by opportunistic agents, hence stressing the importance of T cell adaptive immunity in longevity. These disorders can be cured by allogeneic haematopoietic stem cell transplantation, some by gene therapy while neonatal screening is being developed.
Severe combined immunodeficiencies are rare inherited diseases caused by defective development of the T lymphocyte lineage.
Clinical consequences are devastating leading to death within the first year of life in the absence of treatment.
Allogeneic transplantation of haematopoietic stem cells or in some cases gene therapy can be life saving by restoring T-cell development.
Seventeen different genetic defects have been found to cause SCID, they are classed in six groups as based on pathophysiology.
SCID variants – defined by the presence of residual T cells – are relatively frequent as a consequence of hypomorphic mutation or reversion.
- severe combined immunodeficiencies;
- haematopoietic stem cells;
- T lymphocytes;
- B lymphocytes;
- NK lymphocytes;
- lymphocyte differentiation