Severe combined immunodeficiency disease (XSCID) in Cardigan Welsh Corgi and Pembroke Welsh Corgi

This immune disorder is characterized by reduced lymphocyte counts with low (or absent) concentrations of IgG and IgA, but normal concentrations of IgM. Clinical findings include absence of palpable lymph nodes, small thymus size and chronic recurrent infections. Affected puppies do not thrive well, are plagued by diarrhoea, and occasional vomiting, and even with supportive care usually die by 4 months of age.

The causative mutation in Cardigan Welsh Corgis is a single nucleotide insertion (c.583 _584insC) causing a reading frame shift and subsequent premature termination of the gene encoding IL-2RG, the common gamma chain, which is a subunit of the receptors for the interleukins IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. Functional receptors for these cytokines are essential for leukocyte proliferation, differentiation, survival and function, and their absence causes severe and ultimately lethal disease.

The mutation is X-linked. This means that it is localized on the X chromosome. Males have an X and a Y chromosome, so they can only be healthy (Xn/Y) or affected (Xm/Y). Females have two X chromosomes, so they can either be healthy (Xn/Xn), carriers (Xn/Xm) or affected (Xm/Xm). Female carriers do not show clinical signs but are able to pass the mutant allele to their offspring. Breeding of carrier females is not recommended. The genetic test can clearly reveal the genotype of the animal and is a useful tool for breeders to prevent unintentional breeding of affected puppies.

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References:

Somberg, R.L., Pullen, R.P., Casal, M.L., Patterson, D.F., Felsburg, P.J., Henthorn, P.S. : A single nucleotide insertion in the canine interleukin-2 receptor gamma chain results in X-linked severe combined immunodeficiency disease. Vet Immunol Immunopathol 47:203-13, 1995. Pubmed reference: 8571541