In other species: dog

Categories: Vision / eye phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 613829 (trait) , 602225 (gene)

Links to MONDO diseases:

• MONDO:0013449: Leber congenital amaurosis 7

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal incomplete dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2010

Species-specific name: Progressive retinal dystrophy/atrophy; Cone-rod dystrophy/dysplasia

Species-specific symbol: Rdy

Inheritance: Occelli et al. (2023) report that " the phenotype of CRXRdy/Rdy cats was more severe compared to CRXRdy/+ cats by several metrics." The mode of inheritance was therefore changed from autosomal dominant to incomplete dominant.

Molecular basis: Menotti-Raymond et al. (2010) provided convincing evidence that this form of retinopathy, so long studied, is the result of a frameshift mutation due to a single base deletion in the cone-rod homeobox-containing gene (CRX).

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: Clinically, affected kittens with one copy of the disease allele (CRXRdy/+) can be recognised by the age of 4-5 weeks; they have a slower pupillary light reflex and pupil dilation. 6 weeks old kittens may have a pendular nystagmus, and by 7-8 weeks retinal changes can be observed with ophthalmoscopy in the centralis region. Mottling and grey discolouration of the retina will be observed, and these changes extend to the periphery over a few weeks. By 12 weeks, affected kittens have a generalised hyper-reflectivity of the tapetal fundus, mottling and depigmentation of the non-tapetal area and vascular attenuation. Signs of progressive blindness occur in the first 4 months of life. (Narfström et al., 2011) IT thanks DVM student Jaimie McElroy, who provided the basis of this contribution in May 2023.

Pathology: Occelli et al. (2016) provided a comprehensive description of the pathogenesis in cats that are heterzygous for the frameshift variant (CRXRdy/+) and later reported a more severe phenotype in cats homozygous for the variant (CRXRdy/Rdy) (Occelli et al., 2023): "CRXRdy/Rdy cats had high levels of mutant CRX mRNA and protein. The expression of photoreceptor target genes was severely impaired although there were variable effects on the expression of other transcription factors. The photoreceptor cells remained immature and failed to elaborate outer segments consistent with the lack of retinal function. The retinal layers displayed a progressive remodeling with cell loss but maintained overall retinal thickness due to gliosis. Rapid photoreceptor loss largely occurred in the macula-equivalent retinal region. The homozygous cats developed markedly increased ocular globe length."

Breeds: Abyssinian (Cat) (VBO_0100000), Somali (Cat) (VBO_0100229).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: