The gamma chain gene of the interleukin-2 receptor (IL2RG) is the disease gene for X-linked severe combined immunodeficiency (SCID). This is the most common of several gene defects resulting in the SCID syndrome, which occurs in 1 in 10,000 to 100,000 births. X-linked SCID is generally very severe, with affected males dying of failure to thrive and persistent and opportunistic infections in the first year of life unless they are rescued by bone marrow transplantation. In SCID as in other X-linked lethal conditions, new mutations account for a substantial proportion of cases, and the most common presentation is a sporadic affected male without family history of immune defect. Detection of IL2RG mutations in SCID males is desirable for i) definition of X-linked SCID clinical disease features within the spectrum of all SCID; ii) characterizing specific mutations with regard to frequency and clinical severity; iii) participating in the evolving management of SCID families, including devising and performing carrier and prenatal diagnosis; iii) monitoring utilization of genetic services by families with X-linked SCID; and iv) planning new theraputic approaches. Research efforts have been aimed at mutation detection by single strand conformation polymorphism and dideoxy fingerprinting, with over 60 unrelated patient mutations detected. Unique genetic features including germ line mosaicism, a branch point A mutation and 2 mutational hot spots have been published. Prenatal monitoring of at-risk pregnancies has allowed for implementation of neonatal bone marrow transplantation, with improved results over typical transplants. Moreover, a new and promising prenatal transplantation protocol has been made possible, with a single case to date engrafted at birth with functional paternal lymphocytes after injection intraperitoneally at 17-20 wk of pregnancy with paternal CD34+ cells.
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