Deafness (KLF7-related)

Gene: KLF7

Transmission: Unknown, variable penetration, possibly complex genetics

Mutation: Substitution, KLF7 gene: c.517 C>T, p.(Leu173Phe), exon2, Chr.37.

Medical system: Hearing

Breed: Australian Stumpy Tailed Cattle Dog

Age of onset of symptoms: From birth (congenital)

Deafness is the reduced or absent ability to hear sounds.  It is a common condition in both dogs and humans that can have both genetic (hereditary) and/or environmental causes.  Sensorineural deafness is caused by defects in the inner ear (cochlea) or in the auditory nerve (cranial nerve VIII).  In humans, over 125 genes have been associated with congenital non-syndromic sensorineural deafness, where congenital refers to being present at birth and non-syndromic refers to not being associated with other developmental defects.  In dogs, hereditary deafness has been reported multiple breeds, and numerous genes have been associated with deafness, usually in a breed specific manner (see: PTPRQ, MYO7A, CDH23, LOXHD1, EPS8L2).  Clinically the Brainstem Auditory Evoked Response (BAER) test is a useful non-invasive test for detecting sensorineural deafness. Hereditary deafness in the dog remains a genetically complex disease that will benefit from further research efforts.

The Australian Stumpy Tail Cattle (ASTC) dog is a breed that is known to be susceptible to hereditary deafness, with a breed incidence of over 17%.  Molecular studies were performed on affected and non-affected ASTC dogs and a mutation within the KLF7 gene was shown to be highly associated with the diagnosis of clinical deafness.  The KLF7 gene codes for a transcription factor involved in the development of the nervous system.  Furthermore, the KLF7 gene is expressed in the developing inner ear where it is involved in sensory hair formation.  Thus, the identified mutation in the KLF7 gene in ASTC dogs suffering from deafness is an excellent candidate mutation for the condition, and DNA testing will be useful in selectively breeding out this mutation from the breed.  However, the genetics of deafness in the ASTC dog remains complex, phenotypic penetration of the KLF7 mutation is variable, and there are undoubtedly additional gene mutations that can also be responsible for the clinical deafness observed in the breed.

References:

OMIA link: [2326-9615]

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

Xu F, Shan S, Sommerlad S, et al. (2021) A missense mutation in the KLF7 gene is a potential candidate variant for congenital deafness in Australian Stumpy Tail Cattle dogs. Genes (Basel) 12:467.  [pm/33805165]

Sommerlad S, McRae AF, McDonald B, et al. (2010) Congenital sensorineural deafness in Australian Stumpy-Tail Cattle dogs is an autosomal recessive trait that maps to CFA10. PLoS One 5:e13364. [pm/20967282]

With contributions by:  Audrey Asselin and Carolane Déragon, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).