IL-7 receptor deficient SCID with a unique intronic mutation and post-transplant autoimmunity due to chronic GVHD

Severe combined immunodeficiency (SCID) may result from a variety of genetic defects that impair the development of T cells. Signaling mediated by the cytokine interleukin-7 is essential for the differentiation of T cells from lymphoid progenitors, and mutations of either the interteukin-7 receptor alpha chain (IL-7R alpha) or its associated cytokine receptor chain, the common gamma chain (gamma c), result in SCID. Here we report a case of SCID due to heterozygous mutations of the IL7R gene encoding IL-7R alpha. A previously unrecognized mutation found within intron 3 created a new exon between exons 3 and 4 in the mRNA transcribed from this allele, producing a truncated, unstable mRNA. This mutation illustrates the necessity of evaluating both coding and non-coding regions of genes when searching for pathogenic mutations. Following hematopoietic stem cell transplantation of our patient, immune reconstitution was accompanied by two unusual complications, immune-mediated myositis and myasthenia gravis. (C) 2007 Elsevier Inc. All rights reserved.