title: IL-7 receptor deficient SCID with a unique intronic mutation and post-transplant autoimmunity due to chronic GVHD.
abstract: 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 interleukin-7 receptor alpha chain (IL-7Ralpha) or its associated cytokine receptor chain, the common gamma chain (gammac), result in SCID. Here we report a case of SCID due to heterozygous mutations of the IL7R gene encoding IL-7Ralpha. 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.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Manish J
authors.initials: MJ
authors.lastname: Butte
authors.forename: Charles
authors.initials: C
authors.lastname: Haines
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Bonilla
authors.forename: Jennifer
authors.initials: J
authors.lastname: Puck
mesh_terms: D001483:Base Sequence; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007438:Introns; D008297:Male; D009157:Myasthenia Gravis / Q000276:immunology; D009220:Myositis / Q000276:immunology; D017354:Point Mutation; D020395:Receptors, Interleukin-7 / Q000235:genetics* / Q000276:immunology; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology / Q000628:therapy