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Familial Congenital Methemoglobinemia - Mixed Breed Type
| Acronym: | FCM |
| Gene: | CYB5R3 |
| Mutation: | c.214G>A |
| Inheritance: | Autosomal Recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Familial Congenital Methemoglobinemia is a genetic blood disorder in animals, including dogs, in which an abnormal amount of methemoglobin is produced. Hemoglobin is a protein in red blood cells that carries and distributes oxygen to the body and methemoglobin is one of its forms. High levels of methemoglobin form when hemoglobin iron is oxidized and it cannot efficiently bind and release oxygen. Excess accumulation of methemoglobin in dogs can lead to cyanosis, impaired aerobic respiration, metabolic acidosis, and death in severe cases. Cases of methemoglobinemia reported in dogs are connected to cytochrome b5 reductase deficiency, a protein important for converting methemoglobin back to hemoglobin. The cause of the disorder is a missense mutation in the CYB5R3 gene that encodes cytochrome b5 reductase causing its decreased activity.
This type of methemoglobinemia is found in mixed-breed dogs and is inherited as an autosomal recessive trait meaning two copies of the mutated gene are required for the disease to develop. Dogs with only one copy of the mutated gene will not develop the disease but may act as carriers and pass the mutation to their offspring. There are no long‐term treatment recommendations for affected dogs and that is why early detection by genetic testing is important and can help identify carriers and help breeders in selecting future mating pairs.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Jaffey, J. A., Harmon, M. R., Villani, N. A., Creighton, E. K., Johnson, G. S., Giger, U., & Dodam, J. R. (2017). Long-term Treatment with Methylene Blue in a Dog with Hereditary Methemoglobinemia Caused by Cytochrome b5 Reductase Deficiency. Journal of veterinary internal medicine, 31(6), 1860–1865. https://doi.org/10.1111/jvim.14843
Jaffey, J.A., Harmon, M.R., Villani, N.A., Creighton, E.K., Johnson, G.S., Giger, U., Dodam, J.R. (2017) Long-term treatment with methylene blue in a dog with hereditary methemoglobinemia caused by cytochrome b5 reductase deficiency. J Vet Intern Med. Pubmed reference: 28963729. DOI: 10.1111/jvim.14843.