OMIA:002071-9615 : Macular corneal dystrophy in Canis lupus familiaris
Categories: Vision / eye phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 217800 (trait) , 605294 (gene)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2016
Molecular basis: By sequencing the most likely comparative candidate gene (CHST6) in one affected and one normal Labrador Retriever, Tetas Pont et al. (2016) identified the likely causal mutation as c.814C>A; p.R272S. Supporting evidence was provided by evidence that "six LR affected with MCD were homozygous for the mutant allele, while 140/151 control LR were homozygous for the wild-type allele and 11/151 were heterozygous for the mutation". Frustratingly, CHST6 is called LOC489707 in NCBI Gene.
Clinical features: Busse et al. (2019): "Labrador Retrievers affected by MCD were presented between the age of 4.5 and 6 years of age with a history of cloudy eyes and/or visual impairment. Findings on ophthalmic examination included a diffuse haze of the corneal stroma and multiple, well-demarcated, off-white to yellow-brown, punctate corneal opacities heterogeneous in size. Corneal vascularization developed in most dogs as the disease progressed. Disease progression was associated with increased density of the corneal haze as well as increased number and size of the focal opacities and dogs developed significant visual impairment. Spectral domain-optical coherence tomography revealed multifocal hyper-reflective regions within the stroma. In vivo confocal microscopy revealed marked alterations in reflectivity throughout the entire stroma. Normal keratocytes could not be identified in affected areas."
Pathology: Busse et al. (2019): "Histopathology showed stromal collagen fibers separated by acidophilic granular material on hematoxylin and eosin stain. The material stained with periodic acid-Schiff and colloidal iron stain but not with Masson trichrome stain, confirming the accumulation of glycosaminoglycans. On electron microscopic ultrastructural examination, keratocytes presented with vacuolated rough endoplasmic reticulum and multiple electron dense cytoplasmic inclusions. In areas keratocytes appeared ruptured, with cell organelles and proteinaceous material grouped together between collagen fibers."
Prevalence: As reported by Tetas Pont et al. (2016), "The mutant allele was present in the unrelated LR cohort [of 89 unrelated Labrador Retrievers with unknown clinical status] at a frequency of 0.017, suggesting carrier and affection rates of 3.3% and 0.028%, respectively."
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|LOC489707||carbohydrate sulfotransferase 6||Canis lupus familiaris||5||NC_051809.1 (75580429..75594782)||LOC489707||Homologene, Ensembl , NCBI gene|
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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|
|108||Labrador Retriever||Macular corneal dystrophy||LOC489707||missense||Naturally occurring variant||CanFam3.1||5||g.75279699C>A||c.814C>A||p.(R272S)||2016||26585178||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool|
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.
|2019||Busse, C., Kafarnik, C., Linn-Pearl, R., Volmer, C., Matiasek, K., Premont, J.E., Dulaurent, T., Douet, J.Y., Gilbert, I., Jalomäki, S., Trost, K., Isard, P.F., Boyd, R., Raymond, I. :|
|Phenotype of macular corneal dystrophy in Labrador Retrievers: A multicenter study. Vet Ophthalmol 22:294-304, 2019. Pubmed reference: 30701649 . DOI: 10.1111/vop.12596.|
|2016||Tetas Pont, R., Downs, L., Pettitt, L., Busse, C., Mellersh, C.S. :|
|A Carbohydrate Sulfotransferase-6 (CHST6) gene mutation is associated with Macular Corneal Dystrophy in Labrador Retrievers. Vet Ophthalmol 19:488-492, 2016. Pubmed reference: 26585178 . DOI: 10.1111/vop.12332.|
|2013||Busse, C., Kafarnik, C., Tetas, R. et al. :|
|Case report: A form of macular corneal dystrophy in a Labrador retriever. Abstract presentation in European College of Veterinary Ophthalmologists :, 2013.|
- Changed by Frank Nicholas on 08 Nov 2016
- Created by Frank Nicholas on 08 Nov 2016
- Changed by Frank Nicholas on 26 Oct 2017
- Changed by Frank Nicholas on 18 Jun 2020