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Canine Mendelian disease record

X-Linked Severe Combined Immunodeficiency (Discovered in the Basset Hound; XSCID)

X-Linked Severe Combined Immunodeficiency (Discovered in the Basset Hound; XSCID). X-linked recessive. Observed in 0 of 266 breeds tested in the Sniff Atlas, with measured variant frequencies drawn from 242,665 dogs (Donner 2023). Whether a dog carrying this variant is at risk depends on the disease’s inheritance pattern; outcome also depends on penetrance, modifiers, and environment. The frequencies below describe variant prevalence, not confirmed disease incidence.

OMIA identifier
OMIA:000899-9615
X-linked recessive
Linked gene
IL2RG
Human counterpart
In humans, this gene is IL2RG. OMIM 308380 In people, variants in the IL2RG gene are classified as pathogenic in ClinVar for 2 expert-reviewed conditions.
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human T-B+ severe combined immunodeficiency due to gamma chain deficiency

Dogs with this condition carry a change in IL2RG. In people, changes in the same gene cause T-B+ severe combined immunodeficiency due to gamma chain deficiency. That makes affected dogs a naturally-occurring model of the human disease, and it is part of why studying dogs moves medicine forward for everyone. It does not mean your dog has the human disease. It means the two share an underlying biology.

In people, the disease is described as: Severe combined immunodeficiency (SCID) due to gamma chain deficiency, also called SCID-X1, is a form of SCID characterized by severe and recurrent infections, associated with diarrhea and failure to thrive.

In humans it is also called: SCIDX, SCIDX1, XSCID, severe combined immunodeficiency T- B+, X-linked, severe combined immunodeficiency, X-linked.

MONDO:0010315 OMIM 300400OMIM 312863

Mapped from OMIA via the human disease's OMIM entry to the Mondo Disease Ontology (Monarch Initiative, CC-BY 4.0). Closely related human conditions exist for this gene. Sniff renders this as a model-of link; the canine disease remains the subject of this page.

About this disease

From OMIA's curated record

Documented in OMIA (Online Mendelian Inheritance in Animals). This describes the disease as recorded in the published literature, not a prediction for any individual dog. As of 2026-06-03.

Summary

X-linked severe combined immunodeficiency disease (XSCID) is an immune disorder of basset hounds and Cardigan Welsh corgis. Affected pups have peripheral lymphopenia, with low or absent IgG and IgA, but normal IgM concentrations. Clinical findings include the absence of palpable lymph nodes, a small thymic shadow on radiographs, and chronic recurrent infections. It is invariably lethal. The breed specific mutations in IL2RG lead to production of a truncated protein. Edited by Paula Henthorn, PhD

Clinical features

Affected pups are characterized by failure to thrive, absence of palpable peripheral lymph nodes, small thymic size, and T cells that are unresponsive to proliferative stimulation. Affected pups often succumb to chronic, recurrent, opportunistic infections in varied locations (ear, skin, intestine). Other signs include diarrhea, and intermittent vomiting. Vaccination of affected pups with modified live virus vaccines can induce viremia and clinical signs. Affected pups have peripheral lymphopenia with a normal percentage of B cells and a low to normal percentage of T cells. IgM concentrations are normal, but IgG and IgA concentrations are greatly reduced or absent (Pullen et al., 1997). Even with supportive treatment, affected pups usually die by 4 months of age.

Molecular genetics

By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Henthorn et al. (1994) showed that the causative mutation in basset hounds is a four nucleotide deletion causing a frame shift and subsequent premature termination of the gene coding for the gamma chain of the IL-2 receptor. The causative mutation in the Cardigan Welsh corgi is a single nucleotide insertion causing a frameshift and subsequent premature termination of the gene encoding the gamma chain of the IL-2 receptor (Somberg et al., 1995). There is an analogous disease in humans (OMIM# 300400).

Pathology

IL2RG encodes the common gamma chain, which is a subunit of the receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Functional receptors for these cytokines are necessary for leukocyte proliferation, differentiation, survival and function, and their absence causes a severe and ultimately lethal disease (Kennedy et al., 2011). T cells in affected animals do not proliferate in response to mitogens, such as phytohemagglutin (PHA), because they do not express a functional IL-2 receptor. B cells can produce IgM but cannot class switch to IgG (Felsburg et al, 1999). Primary and secondary lymphoid tissue is either reduced in size or totally absent. At necropsy, the thymus is small and dysplastic (Felsburg et al., 1999).

Prevalence

This disorder is rare.

Control

This is an X-linked trait causing severe disease in very young affected males. Thus, the disease reported in both breeds was likely recognized within a few generations of the occurrence of the initial causative mutation (Pullen et al., 1997). Consequently, the mutation was never widely disseminated in either breed, and breed wide testing is not indicated. However, new cases can occur in any breed due to novel mutations. Rapid referral to a specialist is recommended for suspected cases. Female relatives of affected males should be tested to identify carriers. Breeding of carrier females is not recommended. However, males that are free of the disease do not carry the mutation and can be bred.

Genetic testing

There is a PCR-based test available to detect the mutation in the basset hound and the Cardigan Welsh Corgi.

Human analog

OMIA links this condition to its human counterpart in OMIM (Mendelian Inheritance in Man), the place to read across to the deeper human literature for the same biology.

Disease · OMIM 300400 Disease · OMIM 312863 Gene · OMIM 308380

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:000899-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

Signs & cross-references

How it presents

Catalogued in the Mondo disease ontology (the cross-species disease identity used by the Monarch Initiative) as combined immunodeficiency, X-linked (MONDO:0010730).

Phenotype terms: Human Phenotype Ontology + Mammalian Phenotype Ontology; disease terms: Mondo (Monarch Initiative). Cross-references curated by OMIA (doi:10.25910/2AMR-PV70, CC-BY 4.0).

The evidence

Published references

The peer-reviewed papers behind this disease, curated by OMIA. Starred entries are OMIA-designated landmark papers. Showing 6 of 22.

References curated by OMIA (Nicholas, Tammen & the Sydney Informatics Hub), doi:10.25910/2AMR-PV70 (CC-BY 4.0). Full list at the OMIA entry.

Your breed

See what X-Linked Severe Combined Immunodeficiency (Discovered in the Basset Hound; XSCID) looks like in your dog's breed.
Variant frequency by breed

Observed only in small-sample breeds

Maximum variant frequency per breed across variants in the Donner 2023 cohort, with . The list below is split into well-sampled breeds (n ≥ 50 tested) and small-sample breeds (n < 50, where the Wilson CI typically spans more than 20 percentage points and frequencies should not be compared directly to the well-sampled entries). Frequencies are population-level, not per-litter or per-line.

Scope of this record

Scope

This record carries the breed-level carrier frequencies from the Donner 2023 cohort. Penetrance data (the fraction of at-risk dogs that develop the phenotype) is not yet quantified for this disease in the Sniff Atlas v1.0.1. The OMIA entry is the authoritative reference for the clinical phenotype, inheritance pattern, and gene assignment.

Predicted disease relevance at the per-dog level is UNPROVEN. The variant frequency is measured; phenotype outcome depends on penetrance, environment, and modifier loci. Consult a veterinarian for clinical interpretation.

How to cite this record

Citations

If you use this record in published work, cite the Sniff Atlas (the published dataset that carries the breed-level carrier frequencies) and the upstream sources:

  • Sniff Atlas v1.0.1 for the per-breed carrier frequencies:

    Gehring, M. (2026). Sniff Atlas v1.0.1. Zenodo. https://doi.org/10.5281/zenodo.20566358. CC-BY 4.0.

  • OMIA for the disease definition, inheritance, and gene assignment:

    Nicholas, F. W., & Tammen, I. (2024). OMIA. Sydney Informatics Hub, The University of Sydney. https://doi.org/10.25910/2AMR-PV70. Entry: OMIA:000899-9615.

  • Donner et al. 2023 for the breed × variant carrier-frequency cohort:

    Donner, J., Freyer, J., Davison, S., Anderson, H., Blades, M., Honkanen, L., et al. (2023). Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLOS Genetics, 19(2), e1010651. https://doi.org/10.1371/journal.pgen.1010651.

Full citation formats (BibTeX, RIS, CITATION.cff) at sniff.world/cite.

Related

Related

Last updated
Sources: Sniff Atlas v1.0.1 · OMIA OMIA:000899-9615 · Donner et al. 2023 · ClinVar (Landrum 2018)