Categories: Hearing / vestibular / ear phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 617637 (trait) , 614988 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2022

Species-specific name: Early onset adult deafness

Species-specific symbol: EOAD

Inheritance: Kawakami et al. (2022) reported that "A segregation pattern of this deletion in a 2-generation nuclear family indicated an autosomal recessive mode of inheritance."

Mapping: Kawakami et al. (2022) "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".

Molecular basis: Using "targeted Sanger sequencing analysis" of the CFA18 candidate region, Kawakami et al. (2022) "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."

Clinical features: Kawakami et al. (2022): "Rhodesian Ridgebacks exhibit a progressive postnatal deafness which may be observed as early as four months of age but more commonly observed within 1–2 years after birth . . . . This form of deafness, hereafter referred to as early onset adult deafness (EOAD), does not appear to be restricted to a specific bloodline because it has been identified in multiple Rhodesian Ridgeback populations, including North America, Europe, and Africa. . . . All affected dogs are visually indistinguishable from dogs with normal hearing by having fully pigmented coat, eyes, and noses, indicating that EOAD in Rhodesian Ridgebacks likely has a different genetic basis from pigmentation-related deafness." In their 2022 study, Kawakami et al. "identified 23 EOAD-affected Rhodesian Ridgebacks (11 males and 12 females) that were confirmed deaf by BAER testing; these dogs lost their hearing approximately from 6 months to 24 months after birth. All of the dogs were bilaterally deaf."

Breed: Rhodesian Ridgeback (Dog) (VBO_0201135).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: