Deafness, CDH23-related

Gene: CDH23

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, CDH23 gene: c.700C>T, p.(Pro234Ser), exon8, chromosome 4.

Breed: Beauceron

Medical system: Deafness

Age of onset of symptoms: At birth.

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.  Congenital sensorial deafness was observed in puppies of the Beauceron breed, which is a herding breed originating in central France.  Deafness, diagnosed by behavioral tests and by brainstem auditory evoked response (BAER) testing, was bilateral, non-syndromic and not associated with pigment.  DNA testing identified a mutation in the CDH23 gene, which codes for a protein coding for a transmembrane glycoprotein found on stereocilia of inner ear cells which is involved in converting the mechanical signals of sound waves into nerve signals. Mutations within the CDH23 gene are responsible for sensorial deafness in humans.  Testing of 90 control animals from the Beauceron breed revealed a carrier frequency of 3.3% for the mutation in the CDH23 gene.

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

References:

OMIA link: [2584-9615]

Abitbol M, Jagannathan V, Lopez M, et al. (2023) A CDH23 missense variant in Beauceron dogs with non-syndromic deafness. Anim Genet 54:73-77.  [pm/36308003]

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

McGrath J, Roy P Perrin BJ. (2017) Stereocilia morphogenesis and maintenance through regulation of actin stability.  Sem Cell Dev Biol 65:88-95. [pm/27565685]

Strain GM. (2012) Canine deafness. Vet Clin North Am Small Anim Pract 42:1209-24. [pm/23122177]

Contributed by: Emily Pothier and Julia Vermeulen, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)