A SINGLE NUCLEOTIDE INSERTION IN THE CANINE INTERLEUKIN-2 RECEPTOR-GAMMA CHAIN RESULTS IN X-LINKED SEVERE COMBINED IMMUNODEFICIENCY DISEASE

The immunologic and genetic analysis of a 14-week-old male cardigan We lsh corgi puppy that presented with failure to thrive, diarrhea, and i ntermittent 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 b e responsible for his poor clinical condition. Quantitation of serum i mmunoglobulins 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 contai ned a normal percentage of T cells, with an increased CD4:CD8 ratio, t hey were unable to proliferate in response to phytohemagglutinin (PHA) and/or interleukin 2 (IL-2). Furthermore, following PHA activation, t he peripheral blood lymphocytes (PBL) demonstrated a nearly complete l ack of IL-2 binding. All of these laboratory findings were identical w ith our previous findings from dogs with X-linked severe combined immu nodeficiency (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, resulti ng in a premature stop codon prior to the transmembrane domain. The in sertion also created an EcoO109 restriction enzyme site that enabled u s to detect the mutation in the patient's genomic DNA. This new mutati on in the IL-2R gamma chain discovered in a cardigan Welsh corgi puppy results in XSCID with similar immunologic abnormalities as observed i n dogs with the same disease resulting from a different IL-2R gamma ch ain mutation.