Article

The genetic basis of severe combined immunodeficiency and its variants

The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
The Application of Clinical Genetics 08/2012; 5:67-80. DOI: 10.2147/TACG.S18693
Source: PubMed

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.

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    • "An umbrella term used to cover many austere T-cell primary immunodeficiencies is severe combined immunodeficiency (SCID). The illness is termed severe because it is fatal and is described as combined because although it is often directly T lymphocytes which are affected, B lymphocytes cannot adequately function without the help of T cells and thus both cellmediated and humoural immunity are lost (Tasher and Dalal, 2012). SCID is considered a paediatric emergency with patients appearing well at birth but after a few months, following the subsequent loss of maternal antibody, often present with diarrhoea , sepsis, otitis and an overall failure to thrive (Kelly et al., 2013). "
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