Test Detail

Hereditary complement defect due to deficiency of fraction C3, the third component of the complement cascade. C3 is the central protein of the classical, alternative and lectin pathways, so its absence compromises opsonization and defence against pyogenic bacteria. Affected dogs present recurrent infections and, in the long term, a risk of immune complex disease. It is inherited in a recessive manner.

Specific to the Brittany Spaniel. No reliable carrier figures are published in the general population; the mutation is concentrated in related lines and European data are limited.

- Recurrent bacterial infections (skin, respiratory tract, otitis)
- Growth retardation and poor general condition in puppies
- Increased susceptibility to sepsis
- Risk of immune complex glomerulonephritis with age
- Undetectable or very low serum C3

C3 deficiency was identified in a colony of Brittany Spaniels, being one of the first genetic complement defects described in the canine species; autosomal recessive inheritance and absence of serum C3 were demonstrated (Winkelstein et al., 1981; PMID 7233211). Genetic analysis established that the defect is due to a null gene allelic to the C3 structural gene (Johnson et al., 1986; PMID 3789016). Finally, cloning and sequencing of the canine gene identified the causal mutation: a deletion of a cytosine at position 2136 (codon 712) that causes a frameshift and a stop codon 11 amino acids downstream (Ameratunga et al., 1998; PMID 9510185).

- Test breeding animals before mating
- Do not mate two carriers: 25% risk of affected homozygotes
- A carrier can be mated to a clear animal; test offspring intended for breeding
- Progressively replace carriers with clear offspring without narrowing the gene pool
- Do not spread the allele to lines where it does not exist

Differential diagnosis with other primary immunodeficiencies and with secondary causes of low C3 (consumption due to immune disease or sepsis). Serum C3 measurement is suggestive, but the genetic test confirms carrier status. Monitor renal function in the long term due to the risk of immune complex glomerulopathy.

1. Winkelstein JA, et al. Genetically determined deficiency of the third component of complement in the dog. Science 1981;212(4499):1169-70. PMID: 7233211
2. Johnson JP, et al. Genetic analysis of an inherited deficiency of the third component of complement in Brittany spaniel dogs. Am J Med Genet 1986;25(3):557-62. PMID: 3789016
3. Ameratunga R, et al. Molecular analysis of the third component of canine complement (C3) and identification of the mutation responsible for hereditary canine C3 deficiency. J Immunol 1998;160(6):2824-30. PMID: 9510185
4. OMIA:000155-9615 (C3). https://omia.org/OMIA000155/9615/