Prevalence of Unilateral and Bilateral Deafness in Border Collies and Association with Phenotype

Background:Congenital sensorineural deafness (CSD) occurs in Border Collies, but its prevalence and inheritance are unknown. This study estimated the prevalence of CSD in Border Collies and investigated its association with phenotypic attributes linked to the merle gene, including coat pigmentation and iris color. Hypothesis:Deafness in Border Collies is associated with pigmentation patterns linked to the merle gene. Animals:A total of 2597 Border Collies from the United Kingdom. Methods:A retrospective study of Border Collies tested, during 1994–2002, by using brainstem auditory evoked responses. Associations between deafness and phenotypic attributes were assessed by using generalized logistic regression. Results:The prevalence of CSD in puppies was estimated as 2.8%. The corresponding rates of unilateral and bilateral CSD were 2.3 and 0.5%, respectively. Adjustment for clustering of hearing status by litter reduced the overall prevalence estimate to 1.6%. There was no association between CSD and sex (P= .2). Deaf Border Collies had higher rates of merle coat pigmentation, blue iris pigment, and excess white on the head than normal hearing Border Collies (all P < .001). The odds of deafness were increased by a factor of 14 for Border Collies with deaf dams, relative to the odds for dogs with normal dams (P= .007), after adjustment for phenotypic attributes. Conclusions and Clinical Importance: Associations between CSD and pigmentation patterns linked to the merle gene were demonstrated for Border Collies. Evidence for an inherited component to CSD in Border Collies supports selective breeding from only tested and normal parents to reduce the prevalence of this disease.

Prevalence, heritability and genetic correlations of congenital sensorineural deafness and pigmentation phenotypes in the Border Collie

Congenital sensorineural deafness has been reported frequently in experimental mixed-breed white cats but there is a paucity of data on occurrence of deafness in client-owned pure-breed white cats. To describe hearing status in client-owned pure-breed white cats. Eighty-four pure-breed client-owned cats with white coat color of 10 registered breeds presented for routine hearing evaluation before breeding (1995-2008). Hearing was assessed by click-evoked brainstem auditory evoked response. Overall deafness prevalence was 20.2%; 9 cats (10.7%) were bilaterally deaf and 8 cats (9.5%) were unilaterally deaf. There was no association between sex and deafness status (P= .85). Deafness status was associated with iris color (P= .04). Congenital sensorineural deafness frequently occurs in pure-breed cats with white coat color. Unilateral sensorineural deafness was as common as bilateral deafness.

Congenital sensorineural deafness (CSD) has been reported to affect up to 30% of Dalmatian dogs world-wide and while unilaterally deaf dogs can live a close to normal life, dogs suffering bilateral deafness are frequently euthanized. Extreme-white coat patterning as encoded by the gene Melanocyte Inducing Transcription Factor (MITF) has long been postulated as the major risk factor for CSD in the Dalmatian breed. While attempts to identify causative risk variants associated with CSD have been numerous, no genome-wide association study has positively identified MITF as a risk locus for either bilateral or unilateral deafness in the Dalmatian breed to date. In this study, we identified an association with CSD on CFA20 in the vicinity of MITF within Australian Dalmatian dogs. Although not genome-wide significant, the association signal was validated by reanalysing publicly available data and merging the wider data resource with the local data to improve statistical power. The merged data, representing three major global populations of Dalmatian dogs, enabled us to identify a single, well-defined genome-wide significant risk haplotype for CSD. The haplotype was formed by three genome-wide significant associated markers (BICF2G630233852T>C, BICF2G630233861T>C, BICF2G630233888G>A) on CFA20 with 62% of bilaterally deaf dogs homozygous for the risk haplotype (CCA), while 30% of bilaterally deaf and 45% of hearing dogs carried one copy of the risk haplotype. Animals homozygous or heterozygous for the low-risk haplotype were less likely to be unilaterally deaf. While the association between the risk haplotype and deafness is incomplete, animals homozygous for the risk haplotype were 10-times more likely to be bilaterally deaf. Although the underlying causative variants are yet to be discovered, results from this study can now assist with reducing deafness in Dalmatian dogs.

BackgroundThe English setter (ES) is predisposed to congenital sensorineural deafness (CSD). CSD prevalence and association with phenotype in the UK ES population are previously unreported.MethodsThe database of the authors’ institution...

Congenital sensorineural deafness in Australian Cattle dogs in the UK: Prevalence and association with phenotype

BackgroundData about congenital sensorineural deafness (CSD) in white blue‐eyed cats derive mainly from research colonies, and information about client‐owned cats is limited.ObjectivesTo describe the prevalence of CSD in a client‐owned population of white purebred kittens and colored littermates in the United Kingdom.AnimalsOne hundred thirty‐two solid white client‐owned purebred kittens and 61 colored littermates, 6 to 21 weeks of age.MethodsRetrospective (56 cases) and prospective (137 cases) study. Hearing was assessed by brainstem auditory evoked response testing, and the entire litter was tested.ResultsCongenital sensorineural deafness was diagnosed only in solid white kittens, with a prevalence of 30.3% (15.9% bilateral, 14.4% unilateral). The prevalence of CSD was significantly higher in white kittens with 1 (44.4%) or 2 (50%) blue irises than in those without blue irises (22.2%). Kittens with at least 1 blue iris were 3.2 times more likely to have CSD than kittens without blue irises. In solid white kittens, CSD was diagnosed in 7 of 15 (46.7%) Turkish Vankedisi, 8 of 18 (44.0%) Maine Coon, 18 of 41 (43.9%) Norwegian Forest, 3 of 11 (27.3%) British Shorthair, 2 of 12 (16.7%) Devon Rex, 2 of 12 (8.3%) Persian, 1 of 21 (4.8%) Russian, and 0 of 2 Sphinx. The prevalence of CSD was significantly different in Norwegian Forest, Maine Coon, and Turkish Vankedisi kittens compared with Persian or Russian kittens.Conclusion and Clinical ImportanceWe identified a high prevalence of CSD in a population of client‐owned purebred white kittens in the United Kingdom and suggest differences in breed‐specific prevalence of CSD.

Canine primary closed-angle glaucoma (PCAG) is a complex disease caused by multiple genetic factors. A c.590G>A variant in OLFML3 was recently reported to be a candidate for pectinate ligament abnormality (PLA) and PCAG in the Border Collie. We investigated the association of this variant with PLA and PCAG in Border Collies from the United Kingdom. The OLFML3 variant was genotyped in 106 Border Collies comprising 90 with normal eyes (controls) and 16 with PLA (n=11) and/or PCAG (n=5) (cases). Genotyping was performed in an additional 103 Border Collies to estimate variant frequency within the population. To investigate the association of the variant with disease in other breeds, genotyping was performed in 337 non-Border Collies with PLA and/or PCAG. Of the 90 controls, 71 were homozygous for the wild-type allele, two were homozygous for the variant, and 17 were heterozygous. Of the 16 cases, three were homozygous for the wild-type allele, 11 were homozygous for the variant, and two were heterozygous. The association of the variant allele with disease was significant (P=1.1x10-9 ). We estimated the frequency of this variant to be 4.4% within the United Kingdom Border Collie population, and it was not identified in clinically affected dogs of any other breed. This study confirms the association of the OLFML3 variant with PLA and PCAG in Border Collies from the United Kingdom. DNA testing for the variant and selective breeding can reasonably be expected to result in a reduction of PLA and PCAG prevalence in the breed.

The objective of the present study was to analyze the mode of inheritance for congenital sensorineural deafness (CSD) in German Dalmatian dogs by consideration of association between phenotypic breed characteristics and CSD. Segregation analysis with regressive logistic models was employed to test for different mechanisms of genetic transmission. Data were obtained from all three Dalmatian kennel clubs associated with the German Association for Dog Breeding and Husbandry (VDH). CSD was tested by veterinary practitioners using standardized protocols for Brainstem Auditory-Evoked Response (BAER). The sample included 1899 Dalmatian dogs from 354 litters in 169 different kennels. BAER testing results were from the years 1986 to 1999. Pedigree information was available for up to seven generations. The segregation analysis showed that a mixed monogenic-polygenic model including eye color as covariate among all other tested models best explained the segregation of affected animals in the pedigrees. The recessive major gene segregated in dogs with blue and brown eye color as well as in dogs with and without pigmented coat patches. Models which took into account the occurrence of patches, percentage of puppies tested per litter, or inbreeding coefficient gave no better adjustment to the most general (saturated) model. A procedure for the simultaneous prediction of breeding values and the estimation of genotype probabilities for CSD is expected to improve breeding programs significantly.

Congenital deafness in Jack Russell terriers: Prevalence and association with phenotype

Familial occurrence of retinitis punctata albescens and congenital sensorineural deafness

Analysis of systematic effects on congenital sensorineural deafness in German Dalmatian dogs

The Dogo Argentino dog breed is affected by hereditary congenital sensorineural deafness (CSD) associated with white pigmentation, but prevalence data and associations with phenotypes have not been reported. In a retrospective study, animals were tested by the brainstem auditory evoked response, and phenotype data of sex, iris color, patch presence/absence and parent hearing status were collected. Chi-square analyses were performed to identify associations between deafness and phenotype traits. BAER results and phenotype data were collected for 811 dogs. Hearing status was 74.23% bilaterally hearing, 20.35% unilaterally deaf and 5.43% bilaterally deaf or an overall prevalence of 25.77%. CSD was not associated with sex, but dogs without a patch had a significantly higher prevalence rate than patched dogs. Blue-eyed dogs had higher prevalence rates than brown-eyed dogs, but because of small sample size the χ2 association was not considered valid. Insufficient numbers of dogs with a unilaterally deaf parent were present to assess the effects of parent hearing status. Approximately one fourth of a US Dogo Argentino population was deaf in one or both ears, but dogs with a patch had a lower prevalence. Dogs with a blue eye were more likely to be deaf, but the association significance could not be reliably assessed.

Functional defects of the mitochondrial translation machinery, as a result of mutations in nuclear-encoded genes, have been associated with combined oxidative phosphorylation (OXPHOS) deficiencies. We report siblings with congenital sensorineural deafness and lactic acidemia in association with combined respiratory chain (RC) deficiencies of complexes I, III and IV observed in fibroblasts and liver. One of the siblings had a more severe phenotype showing progressive hepatic and renal failure. Whole-exome sequencing revealed a homozygous mutation in the gene encoding mitochondrial ribosomal protein S7 (MRPS7), a c.550A>G transition that encodes a substitution of valine for a highly conserved methionine (p.Met184Val) in both affected siblings. MRPS7 is a 12S ribosomal RNA-binding subunit of the small mitochondrial ribosomal subunit, and is required for the assembly of the small ribosomal subunit. Pulse labeling of mitochondrial protein synthesis products revealed impaired mitochondrial protein synthesis in patient fibroblasts. Exogenous expression of wild-type MRPS7 in patient fibroblasts rescued complexes I and IV activities, demonstrating the deleterious effect of the mutation on RC function. Moreover, reduced 12S rRNA transcript levels observed in the patient's fibroblasts were also restored to normal levels by exogenous expression of wild-type MRPS7. Our data demonstrate the pathogenicity of the identified MRPS7 mutation as a novel cause of mitochondrial RC dysfunction, congenital sensorineural deafness and progressive hepatic and renal failure.

BackgroundData regarding congenital sensorineural deafness (CSD) in client‐owned, white Devon Rex cats is limited because most of the information on this disease comes from experiments on mixed‐breed cats.ObjectivesProvide data on the occurrence of CSD in a population of client‐owned purebred white Devon Rex cats.AnimalsForty client‐owned, purebred, white Devon Rex cats examined at 2 different facilities. Median age of the examined cats was 19 weeks.MethodsHearing status was defined by use of brainstem auditory evoked responses.ResultsThe occurrence of sensorineural deafness in the studied population of Devon Rex cats was estimated at 10%. Unilateral and bilateral deafness occurred equally often, with 2 individuals having each (ie, 5.0%). No association between the occurrence of CSD and sex could be found, χ2 (1, n = 40) = 0.001 (P > .99). No association between blue irises and deafness was noted in the studied population, χ2 (1, n = 40) < 0.01 (P > .99).ConclusionsThe occurrence of CSD in a population of client‐owned, white Devon Rex cats was found to be lower compared with data obtained in previously conducted studies of deafness in purebred cats. In the studied population of Devon Rex cats, no association between blue irises and CSD was found.