title: A single nucleotide insertion in the canine interleukin-2 receptor gamma chain results in X-linked severe combined immunodeficiency disease.
abstract: The immunologic and genetic analysis of a 14-week-old-male cardigan Welsh corgi puppy that presented with failure to thrive, diarrhea, and intermittent vomiting are described. The lack of palpable lymph nodes, the premature death of a male sibling, and similar clinical signs in a male cousin suggested that a primary immunodeficiency disease might be responsible for his poor clinical condition. Quantitation of serum immunoglobulins revealed low concentrations of IgG and undetectable IgA, yet normal concentrations of IgM. A complete blood cell count showed a slight anemia and lymphopenia. Although the peripheral blood contained a normal percentage of T cells, with an increased CD4:CD8 ratio, they were unable to proliferate in response to phytohemagglutinin (PHA) and/or interleukin 2 (IL-2). Furthermore, following PHA activation, the peripheral blood lymphocytes (PBL) demonstrated a nearly complete lack of IL-2 binding. All of these laboratory findings were identical with our previous findings from dogs with X-linked severe combined immunodeficiency (XSCID) that is due to a mutation in their IL-2 receptor gamma (IL-2R gamma) chain. Examination of the corgi's IL-2R gamma cDNA revealed an insertion of a cytosine following nucleotide 582, resulting in a premature stop codon prior to the transmembrane domain. The insertion also created an EcoO109 restriction enzyme site that enabled us to detect the mutation in the patient's genomic DNA. This new mutation in the IL-2R gamma chain discovered in a cardigan Welsh corgi puppy results in XSCID with similar immunologic abnormalities as observed in dogs with the same disease resulting from a different IL-2R gamma chain mutation.
authors.affiliation: Department of Clinical Studies, University of Pennsylvania, School of Veterinary Medicine, Philadelphia 19104-6010, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Somberg
authors.forename: R P
authors.initials: RP
authors.lastname: Pullen
authors.forename: M L
authors.initials: ML
authors.lastname: Casal
authors.forename: D F
authors.initials: DF
authors.lastname: Patterson
authors.forename: P J
authors.initials: PJ
authors.lastname: Felsburg
authors.forename: P S
authors.initials: PS
authors.lastname: Henthorn
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004283:Dog Diseases / Q000235:genetics* / Q000276:immunology; D004285:Dogs; D005434:Flow Cytometry / Q000662:veterinary; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D017098:IgA Deficiency / Q000235:genetics / Q000276:immunology / Q000662:veterinary; D017099:IgG Deficiency / Q000235:genetics / Q000276:immunology / Q000662:veterinary; D016130:Immunophenotyping / Q000662:veterinary; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000662:veterinary; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D013601:T-Lymphocytes / Q000276:immunology; D014960:X Chromosome / Q000235:genetics
chemical_list: D015375:Receptors, Interleukin-2