Necrotizing myelopathy

Gene: IBA57

Transmission: Autosomal recessive

For an autosomal recessive genetic disease, an animal must have two copies of the mutation in question to be at risk of developing the disease. Both parents of an affected animal must be carriers of at least one copy of the mutation. Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, IBA57 gene; c.439C>T, p.(R147W), chr.14.

Medical system: Neurological

Breeds: Kooikerhondje

Age of onset of symptoms: From 3 to 12 months of age.

Hereditary necrotising myelopathy is a neurological genetic disease seen in the Dutch Kooiker dog for more than fifty years. Clinical signs begin with mild to moderate muscle weakness (paresis) seen at three to twelve months of age, exaggerated spinal reflexes, an ataxia of the hindlimbs that progresses to the forelimbs, culminating in tetraparalysis by two years of age and usually resulting in humanitarian euthanasia. On necropsy, a bilateral necrotizing myelopathy is seen in both ventral and dorsal white matter of the spinal cord. Molecular studies identified a mutation in the IBA57 gene, which is a nuclear gene that codes for a mitochondrial protein involved in metabolic processes of the respiratory chain. Cells of the central nervous system are particularly sensitive to deregulated IBA57 gene function, resulting in the neurodegenerative necrotizing myelopathy phenotype seen in both humans and the Kooiker dog.

The availability of a DNA test for the IBA57 mutation will now help breeders to identify carrier animals, so that they may use selective breeding to eliminate the disease and eventually the mutation from their breed.

References:

Lien OMIA : [0706-9615]

Mandigers PJJ, Stehling O, Vos-Loohuis M, et al. (2023) A novel IBA57 variant is associated with mitochondrial iron-sulfur protein deficiency and necrotizing myelopathy in dogs. Front Genet 14:1190222. [pm/37588046]

Mandigers PJJ, Vannes JJ, Knol BW, et al. (1993) Hereditary necrotising myelopathy in Kooiker dogs. Research in Veterinary Science 54:118-123. [pm/8434139]

Contributed by: Alice Hébert and Lauren Ding, Class of 2028, Faculty of Veterinary Medicine, University of Montreal. (Translation DWS).