The genetic basis of severe combined immunodeficiency and its variants

enetic basis of severe combined immunodeficiency and its variants Review (1943) Total Article Views Authors: Tasher D, Dalal I Published Date August 2012 Volume 2012:5 Pages 67 - 80 DOI: http://dx.doi.org/10.2147/TACG.S18693 Received: 10 February 2012 Accepted: 12 March 2012 Published: 07 August 2012 Diana Tasher,1,2 Ilan Dalal1,2 1The Pediatric Infectious and Immunology Unit, E Wolfson Medical Center, Holon, Israel; 2The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel Abstract: Severe combined immunodeficiency (SCID) syndromes are characterized by a block in T lymphocyte differentiation that is variably associated with abnormal development of other lymphocyte lineages (B and/or natural killer [NK] cells), leading to death early in life unless treated urgently by hematopoietic stem cell transplant. SCID comprises genotypically and phenotypically heterogeneous conditions, of which the genetic basis for approximately 85% of the underlying immunologic defects have been recently elucidated. A major obstacle in deciphering the pathogenesis of SCID syndromes is that different mutations in a single gene may give rise to distinct clinical conditions and that a similar clinical phenotype can result from mutations in different genes. Mutation analysis is now an important component of the complete evaluation of a patient with SCID since it has a dramatic impact on many aspects of this potentially life-threatening disease such as genetic counseling, prenatal diagnosis, modalities of treatment, and, eventually, prognosis. Dr Robert Good, one of the founders of modern immunology, described the SCID syndrome as "experiments of nature." By understanding the cellular and genetic basis of these immunodeficiency diseases and, eventually, normal immunity, we optimize the "bedside to research laboratory and back again" approach to medicine.