A CDH23 missense variant in Beauceron dogs with non-syndromic deafness

• Published in: Animal Genetics
• Main Authors: Abitbol, Marie, Jagannathan, Vidhya, Lopez, Marie, Courtin, Ambre, Dufaure de Citres, Caroline, Gache, Vincent, Leeb, Tosso
• Other Authors: VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universität Bern = University of Bern = Université de Berne (UNIBE), École nationale vétérinaire d'Alfort (ENVA), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Société Centrale Canine, Partenaires INRAE, Antagene France, Collaboration internationale
• Format: Article in Journal/Newspaper
• Language: English
• Published: CCSD 2023
• Subjects: Canis lupus familiaris; DFNB12; Usher syndrome; cadherin; canine; hearing loss; [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health; Merle; Canis lupus
• Online Access: https://enva.hal.science/hal-03854349; https://enva.hal.science/hal-03854349v1/document; https://enva.hal.science/hal-03854349v1/file/main.pdf; https://doi.org/10.1111/age.13273

International audience Congenital coat-colour-related deafness is common among certain canine breeds especially those exhibiting extreme white spotting or merle patterning. We identified a non-syndromic deafness in Beauceron dogs characterised by a bilateral hearing loss in puppies that is not linked to coat colour. Pedigree analysis suggested an autosomal recessive transmission. By combining homozygosity mapping with whole genome sequencing and variant filtering in affected dogs we identified a CDH23:c.700C>T variant. The variant, located in the CHD23 (cadherin related 23) gene, was predicted to induce a CDH23:p.(Pro234Ser) change in the protein. Proline-234 of CDH23 protein is highly conserved across different vertebrate species. In silico tools predicted the CDH23:p.(Pro234Ser) change to be deleterious. CDH23 encodes a calcium-dependent transmembrane glycoprotein localised near the tips of hair-cell stereocilia in the mammalian inner ear. Intact function of these cilia is mandatory for the transformation of the acoustical wave into a neurological signal, leading to sensorineural deafness when impaired. By genotyping a cohort of 90 control Beauceron dogs sampled in France, we found a 3.3% carrier frequency. The CDH23:c.[700C>T] allele is easily detectable with a genetic test to avoid at-risk matings.