Congenital hypothyroidism (CHG) in Spanish Water Dogs

Reduced thyroid function (hypothyroidism) is one of the most common endocrine diseases affecting both humans and many animals, including dogs. It is a complex clinical condition that is caused by a combination of genetic and environmental factors.

In primary congenital hypothyroidism, the onset of clinical symptoms is early (within one week of age). Symptoms include lethargy, inability to suck, growth retardation (dwarfism), vertebral and limb dysplasia, thickened subcutaneous tissue, delayed teething, delayed opening of the eyes and ear canals, and delayed hair growth. Thyroid cells undergo hypertrophy and hyperplasia, leading to goiter (enlarged thyroid gland).

One of the two causative variants discovered so far in dogs is a mutation in the thyroid peroxidase (TPO) gene. TPO is the enzyme responsible for binding iodide to thyroglobulin, a necessary step in thyroid hormone synthesis.

A single guanosine insertion was observed in the first exon of the TPO cDNA (c.39_40insG) in the affected Spanish Water Dogs.

CHG is a recessively inherited disease. The disease develops in dogs which inherit the mutated gene from each parent.  These dogs are designated as P/P (positive/positive). The carriers of the mutated gene are designated as N/P (negative/positive). The carriers inherited the mutated gene from one parent only and are without clinical signs. However, they pass the disease on to their offspring.  When mating two heterozygotes (N/P), there will be theoretically 25% of the offspring healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will be affected by CHG.  Mating one healthy dog (N/N) with a carrier of this mutation (N/P) will theoretically produce 50% carriers and 50% healthy offspring.  If a carrier (N/P) is mated with an affected dog (P/P), there will be theoretically 50% affected dogs and 50% carriers.

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References:

Bianchi, M., Dahlgren, S., Massey, J., Dietschi, E., Kierczak, M., Lund-Ziener, M., Sundberg, K., Thoresen, S.I., Kämpe, O., Andersson, G., Ollier, W.E., Hedhammar, Å., Leeb, T., Lindblad-Toh, K., Kennedy, L.J., Lingaas, F., Rosengren Pielberg, G. : A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12. PLoS One 10:e0134720, 2015. Pubmed reference: 26261983