Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 217800 (trait) , 605294 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0009020: macular corneal dystrophy

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: 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."

Breed: Labrador Retriever (Dog) (VBO_0200800).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: