In other species: pig

Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 248200 (trait) , 601691 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0019353: Stargardt disease

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2019

Species-specific name: Retinal atrophy - generalized; retinal atrophy, ABCA4-related

Molecular basis: Mäkeläinen et al. (2019): "To study a novel form of retinal degeneration in Labrador retriever dogs with clinical signs indicating cone and rod degeneration, we used whole-genome sequencing [WGS] of an affected sib-pair and their unaffected parents. A frameshift insertion in the ATP binding cassette subfamily A member 4 (ABCA4) gene (c.4176insC), leading to a premature stop codon in exon 28 (p.F1393Lfs*1395), was identified." These same authors genotyped "eight additional clinically affected and fourteen unaffected Labrador retrievers. Out of these 22 dogs, 16 were related to the family quartet used in the WGS . . . . all eight affected individuals were homozygous for the ABCA4 insertion and the 14 unaffected individuals were either heterozygous or homozygous for the wild-type allele".

Clinical features: Mäkeläinen et al. (2019): "The affected sib-pair . . . was visually impaired under both daylight and dimlight conditions when examined at 10 years of age. Their pupils were dilated under daylight conditions and pupillary light and dazzle reflexes were abnormal, whereas menace responses were present. On indirect ophthalmoscopy, the tapetal reflectivity varied between normal to grayish hyporeflection when the indirect ophthalmoscopy lens was tilted slightly back and forth, both in the visual streak, as well as in the more peripheral parts of the tapetal fundus in both eyes of the affected dogs. The visual streak is an area of high photoreceptor cell density in the canine retina, located superior to the optic disc and extending horizontally from the nasal to the temporal region . . . . Furthermore, a mild to moderate vascular attenuation was observed, as seen in the fundus photograph, taken at the age of 10 years, of the affected male (LAB4) and compared to a fundus photograph of an unaffected, age-matched Labrador retriever dog (LAB27) . . . . These ophthalmoscopic findings were symmetrical between the eyes of the affected dogs, diffusely spread over the tapetal fundus and not strictly confined to the visual streak or area centralis." Ekesten et al. (2022) studied "retinal appearance and morphology in Labrador retrievers (LRs) heterozygous and homozygous for an ABCA4 loss-of-function mutation. ... Abnormal appearance and morphology in the fovea equivalent are present in juvenile ABCA4InsC/InsC. In the older affected LRs, the visual streak and then the peripheral retina also develop an abnormal appearance. Vision deteriorates slowly, but some vision is retained throughout life. Older heterozygotes may show a mild retinal phenotype but no obvious visual impairment."

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: