Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 606045 (gene) , 218330 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2021

Species-specific description: Kaukonen et al. (2021): "Retinitis pigmentosa (RP) is a blinding eye disease affecting nearly two million people worldwide. Dogs are affected with a similar illness termed progressive retinal atrophy (PRA). Lapponian herders (LHs) are affected with several types of inherited retinal dystrophies, and variants in PRCD and BEST1 genes have been associated with generalized PRA and canine multifocal retinopathy 3 (cmr3), respectively. However, all retinal dystrophy cases in LHs are not explained by these variants ... . We report here a recessive missense variant in IFT122 as a candidate causal variant for a novel canine RP model ... ."

Inheritance: Kaukonen et al. (2021): "Pedigree analysis suggested autosomal recessive PRA in LH [Lapponian Herders], as affected dogs were born to unaffected individuals, there were multiple cases in one of the affected litters, and both sexes were equally affected."

Mapping: Kaukonen et al. (2021) "collected DNA samples from 10 PRA affected LHs [Lapponian Herders], with known PRCD and BEST1 variants excluded, and 34 unaffected LHs. A genome-wide association study identified a locus on CFA20 (praw = 2.4 × 10–7, pBonf = 0.035) ."

Molecular basis: Kaukonen et al. (2021): "whole-genome sequencing of an affected LH [Lapponian Herders] revealed a missense variant, c.3176G>A, in the intraflagellar transport 122 (IFT122) gene. The variant was also found in Finnish Lapphunds, in which its clinical relevancy needs to be studied further. The variant interrupts a highly conserved residue, p.(R1059H)."

Clinical features: Kaukonen et al. (2021): "examinations had revealed clinical findings compatible with generalized PRA in 10 LHs (five males, five females), as these dogs presented with bilateral, diffuse tapetal hyperreflectivity and vessel attenuation. Two of the 10 cases were only examined as young or middle-aged adults (at 1.9 and 5.1 years of age) when they exhibited only mild fundus changes and were therefore diagnosed to have “PRA suspected”. The remaining eight dogs were also examined later in life and had been diagnosed as “PRA affected” at an average age of 9.0 years (± SD 2.9). Typical early findings included night blindness and diffuse tapetal hyperreflectivity. Disease progression was slow as some of the affected dogs still had some visual capacity left at 13 years. All the cases were genotyped for the PRCD p.C2Y and the cmr3 (p.P463fs, p.G489V) variants ... . Of the 10 cases, all were wild-type for the PRCD variant, while four were wild-type and six heterozygous for the two cmr3 variants ... . Spectral-domain optical coherence tomography (SD-OCT) was performed ... . The thicknesses of the whole retina with the retinal pigment epithelium (RPE) and outer retinal layers, including outer nuclear layer, inner segments and outer segments of photoreceptors, and RPE, were severely reduced in the affected dog ... . Interestingly, the photoreceptor layer was not completely lost despite the dog’s old age ... . Apart from the ocular signs, all three dogs were clinically healthy."

Breeds: Finnish Lapphund (Dog) (VBO_0200523), Lapponian Herder (Dog) (VBO_0200814).
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: