OMIA 002071-9615 : Macular corneal dystrophy in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 217800 (trait) , 605294 (gene)

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."

Associated gene:

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

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
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

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.
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.

Edit History


  • Created by Frank Nicholas on 08 Nov 2016
  • Changed by Frank Nicholas on 08 Nov 2016
  • Changed by Frank Nicholas on 26 Oct 2017
  • Changed by Frank Nicholas on 18 Jun 2020