X-linked form of canine severe combined immunodeficiency caused by a defect in the common gamma chain of the cytokine receptor (IL2RG). Affected males lack functional T lymphocytes and have defective humoral immunity, and die from opportunistic infections in the first months. It is the natural canine model of human X-SCID and has been key in the development of gene therapy. Independent mutations have been described in the Basset Hound and the Cardigan Welsh Corgi.

The Basset Hound is the best-characterised breed; the Cardigan Welsh Corgi has an independent mutation. The disease is rare in both breeds and no reliable carrier frequency figures are available for the general population.

- Suckling males with failure to thrive
- Recurrent pneumonia, diarrhoea and otitis
- Functional absence of thymus and T lymphopenia
- Mortality before 4 months of age without treatment

Canine X-SCID was one of the first natural models of human immunodeficiency. Henthorn et al. (1994) identified in the Basset Hound a 4-bp deletion in exon 1 of IL2RG that prevents the production of functional protein, demonstrating that the canine disease is a true homologue of human X-SCID. Somberg et al. (1995) described in a Cardigan Welsh Corgi puppy a different mutation: the duplication of a cytosine (c.583dup) that generates a premature stop codon. The canine model served as the basis for the pioneering gene therapy trials for X-SCID.

- Genotype females from affected lines before mating
- Do not mate carrier females with males from mutant lines
- Prioritise clear breeding animals to eliminate the X-linked allele
- Affected males must not be used as breeding animals
- A clear male mated to carrier females produces 50% carrier daughters: test the offspring

Differential diagnosis with autosomal SCID (PRKDC) of the Jack Russell Terrier. Experimental gene therapy was historically evaluated in the canine model before in humans. Confirm the breed (Basset Hound vs. Cardigan Welsh Corgi) before interpreting the variant, since the IL2RG mutations differ in each.

1. Henthorn PS et al. (1994) IL-2R gamma gene microdeletion demonstrates that canine X-linked severe combined immunodeficiency is a homologue of the human disease. Genomics 23:69-74. PMID: 7829104
2. Somberg RL et al. (1995) 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. PMID: 8571541
3. OMIA:000899-9615. Severe combined immunodeficiency disease, X-linked in Canis lupus familiaris. https://omia.org/OMIA000899/9615/