Categories: Hearing / vestibular / ear phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 604865 (gene)

Mendelian trait/disorder: unknown

Disease-related: yes

Year key variant first reported: 2021

Species-specific name: Congenital Deafness; hearing loss; canine deafness; congenital sensorineural deafness

Mapping: Xu et al. (2021): "performed a genome-wide association study (GWAS) and whole genome sequencing (WGS) of affected and normal individuals. For GWAS, 3 bilateral deaf ASCDs [Australian stumpy tail cattle dogs], 43 herding dogs, and one unaffected ASCD were used, resulting in 13 significantly associated loci on 6 chromosomes, i.e., CFA3, 8, 17, 23, 28, and 37. CFA37 harbored a region with the most significant association (−log10(9.54 × 10−21) = 20.02) as well as 7 of the 13 associated loci."

Molecular basis: Xu et al. (2021): "For whole genome sequencing, the same three affected ASCDs [Australian stumpy tail cattle dogs] and one unaffected ASCD were used. ... Using effect prediction tools, two variants remained with predicted deleterious effects within the Heart development protein with EGF like domains 1 (HEG1) gene (NC_006615.3: g.28028412G>C; XP_022269716.1: p.His531Asp) and Kruppel-like factor 7 (KLF7) gene (NC_006619.3: g.15562684G>A; XP_022270984.1: p.Leu173Phe). Due to its function as a regulator in heart and vessel formation and cardiovascular development, HEG1 was excluded as a candidate gene. On the other hand, KLF7 plays a crucial role in the nervous system, is expressed in the otic placode, and is reported to be involved in inner ear development. 55 additional ASCD samples (28 deaf and 27 normal hearing dogs) were genotyped for the KLF7 variant, and the variant remained significantly associated with deafness in ASCD (p = 0.014). Furthermore, 24 dogs with heterozygous or homozygous mutations were detected, including 18 deaf dogs. The penetrance was calculated to be 0.75 ...."

Breed: Australian Stumpy Tail Cattle Dog (Dog) (VBO_0200097).
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: