OMIA 002336-9615 : Deafness, LOXHD1-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 613079 (trait) , 613072 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2021

Species-specific name: Nonsyndromic hearing loss

Inheritance: Hytönen et al. (2021): "To validate the LOXHD1 variant, we genotyped it in a cohort of 585 Rottweilers, including the four affected siblings and 581 unaffected dogs. We observed complete segregation of the variant with hearing loss, as all four affected dogs were homozygous for the variant. The unaffected dogs were either heterozygous (n = 33) or wild-type (n = 548). The six unaffected littermates of the probands were either wild-type or heterozygous for the variant."

Molecular basis: Using "a combined approach of homozygosity mapping and genome sequencing to dissect the genetic background of the disorder . . . . [Hytönen et al. (2021)] identified a fully segregating missense variant [chr7:44,806,821G>C; p.(G1914A)] in LOXHD1, a gene that is known to be essential for cochlear hair cell function and associated with nonsyndromic hearing loss in humans and mice."

Clinical features: Hytönen et al. (2021): "Sensorineural bilateral deafness was diagnosed in four Rottweiler siblings (one female and three males) in a litter of ten puppies using brainstem auditory evoked response (BAER) testing. BAER testing was performed either at 4 (n = 2), 5, or 19 months of age, and no auditory response was detected in any of them. However, owners’ observations suggested that the puppies had already been affected by hearing impairment at a few weeks of age. No other clinical signs were observed."

Prevalence: Hytönen et al. (2021): "The allele frequency in the population [of Rottweilers], excluding the affected family, was 2.6% and carrier frequency 5.3%. An additional sample of dogs submitted for commercial genetic testing was screened for the LOXHD1 variant to explore its distribution across breeds. All 28,116 tested dogs representing 374 breeds, breed varieties or designer dog mixes were found homozygous for the wild-type allele (Online Resource 7). Finally, the variant was also screened in a larger study sample of 771,864 dogs submitted to genetic testing, including breed detection assessment. A variant carrier frequency of 0.08% and allele frequency of 0.04% were observed in this dataset. Interestingly, six dogs were found homozygous for the LOXHD1 variant. We were able to contact the owners of 4/6 of the homozygous dogs and the owners reported profound hearing loss or deafness in all of them. One of the deaf dogs did not show any immediate Rottweiler ancestry, while one was a purebred Rottweiler and two were mixed-breed with Rottweiler ancestry. Altogether, of the dogs carrying at least one copy of the deafness candidate variant, 63.4% showed evidence of Rottweiler ancestry in their immediate three-generation pedigree going back to great-grandparents, providing further support for a link between this specific breed background and the presence of the variant."

Breed: Rottweiler.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
LOXHD1 lipoxygenase homology domains 1 Canis lupus familiaris 7 NC_051811.1 (44615788..44781462) LOXHD1 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
1314 Rottweiler Nonsyndromic hearing loss LOXHD1 missense Naturally occurring variant CanFam3.1 7 g.44806821G>C c.5747G>C p.(G1914A) XM_022421426.1, c.5747G>C; J9PAE4, p.(G1914A) (Hytönen et al., 2021) 2021 33983508

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2021 Hytönen, M.K., Niskanen, J.E., Arumilli, M., Brookhart-Knox, C.A., Donner, J., Lohi, H. :
Missense variant in LOXHD1 is associated with canine nonsyndromic hearing loss. Hum Genet 140:1611-18, 2021. Pubmed reference: 33983508. DOI: 10.1007/s00439-021-02286-z.
2001 Coppens, A.G., Kiss, R., Heizmann, C.W., Deltenre, P., Poncelet, L. :
An original inner ear neuroepithelial degeneration in a deaf Rottweiler puppy. Hear Res 161:65-71, 2001. Pubmed reference: 11744282. DOI: 10.1016/s0378-5955(01)00354-9.
1996 Strain, G.M. :
Aetiology, prevalence and diagnosis of deafness in dogs and cats [Review] British Veterinary Journal 152:17-36, 1996. Pubmed reference: 8634862.

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  • Created by Frank Nicholas on 15 May 2021