Early onset adult deafness in the Rhodesian Ridgeback dog is associated with an in-frame deletion in the EPS8L2 gene

PLoS One. 2022 Apr 6;17(4):e0264365. doi: 10.1371/journal.pone.0264365. eCollection 2022.


Domestic dogs exhibit diverse types of both congenital and non-congenital hearing losses. Rhodesian Ridgebacks can suffer from a progressive hearing loss in the early stage of their life, a condition known as early onset adult deafness (EOAD), where they lose their hearing ability within 1-2 years after birth. In order to investigate the genetic basis of this hereditary hearing disorder, we performed a genome-wide association study (GWAS) by using a sample of 23 affected and 162 control Rhodesian Ridgebacks. We identified a genomic region on canine chromosome 18 (CFA18) that is strongly associated with EOAD, and our subsequent targeted Sanger sequencing analysis identified a 12-bp inframe deletion in EPS8L2 (CFA18:25,868,739-25,868,751 in the UMICH_Zoey_3.1/canFam5 reference genome build). Additional genotyping confirmed a strong association between the 12-bp deletion and EOAD, where all affected dogs were homozygous for the deletion, while none of the control dogs was a deletion homozygote. A segregation pattern of this deletion in a 2-generation nuclear family indicated an autosomal recessive mode of inheritance. Since EPS8L2 plays a critical role in the maintenance and integrity of the inner ear hair cells in humans and other mammals, the inframe deletion found in this study represents a strong candidate causal mutation for EOAD in Rhodesian Ridgebacks. Genetic and clinical similarities between childhood deafness in humans and EOAD in Rhodesian Ridgebacks emphasizes the potential value of this dog breed in translational research in hereditary hearing disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Deafness* / genetics
  • Deafness* / veterinary
  • Dog Diseases* / genetics
  • Dogs
  • Genome-Wide Association Study
  • Hearing Loss* / genetics
  • Hearing Loss* / veterinary
  • Mammals / genetics
  • Sequence Deletion

Grants and funding

This study was funded by Embark Veterinary, Inc. and the participants that provided DNA and phenotypic information via Embark’s web-based platform. The funder only provided financial support in the form of salaries for all authors but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.