Early Onset Adult Deafness (EOAD), EPS8L2-related

Gene: EPS8L2

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: Deletion, EPS8L2 gene; c.1033_1044 del12nt, p.(Val345_Leu348del), exon12, chromosome 18.

Breed: Rhodesian Ridgeback

Medical system: Deafness

Age of onset of symptoms: 1 to 2 years.

Deafness in dogs, as in humans, can have both genetic and environmental causes. Genetic lesions can manifest as congenital deafness (present at birth), early onset deafness which progressively affects adolescent and early adult animals, or late onset deafness which affects mature animals. An early adult onset deafness (EAOD) is observed in Rhodesian Ridgebacks, with clinical signs of auditory defects occurring between 1 to 2 years of age. This deafness is bilateral, progressive, not syndromic nor associated with pigmentation, and occurs equally between the sexes. Brainstem auditory evoked response (BAER) testing of susceptible animals can begin detecting auditory defects as early as by 4 months. The disease appears widespread as it has been identified in multiple Rhodesian Ridgeback populations. DNA tests revealed a deletion mutation within the EPS8L2 gene, which codes for a protein involved in growth factor receptor function and which is needed for the maintenance of inner ear hair cells. Representative frequencies of the mutation within the Rhodesian Ridgeback breed await further studies.

Veterinarians and breeders of Rhodesian Ridgeback should now use DNA testing and selective breeding to reduce and eventually eliminate the disease and the mutation within this breed.

References:

OMIA link: [2550-9615]

Cocostîrc V, Paștiu AI, Pusta DL. (2023) An overview of canine inherited neurological disorders with known causal variants. Animals (Basel) 13:3568. [pm/38003185]

Kawakami T, Raghavan V, Ruhe AL, et al. (2022) Early onset adult deafness in the Rhodesian Ridgeback dog is associated with an in-frame deletion in the EPS8L2 gene. PLoS One 17:e0264365. [pm/35385474]

Strain GM. (2015) The genetics of deafness in domestic animals. Front Vet Sci 2:29. [pm/26664958]
Strain GM. (2012) Canine deafness. Vet Clin North Am Small Anim Pract 42:1209-24. [pm/23122177]

Contributed by: Benjamin Laboissonnière and Audrey Veilleux, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal. (Translation DWS)