Genetic Defects Associated with SCID and Their Impact on Lymphocyte Development

Lymphocyte development is a tightly coordinated process that is orchestrated by a precise sequence of steps regulated by a variety of molecular players. The alteration of one or more of the molecules that regulate this process can irreversibly affect the correct development of the lymphocytic populations, resulting in milder or more severe forms of immunodeficiencies. This is the case of severe combined immunodeficiency (SCID), a severe primary immunodeficiency characterized by defective T lymphocyte development, in some cases associated with a defect in either B-lymphocyte or natural killer cell (NK) development. A large panel of genetic defects have been associated with SCID over the years; in this chapter, we describe the main ones, focusing on their implication in the developmental processes lead to the generation of functional B and T lymphocytes, as well as NK cells. The characterization of gene defects in SCID and the associated clinical phenotypes have important implications in the diagnosis and the therapeutic management of SCID patients.