OMIA 002320-9615 : Progressive retinal atrophy, IFT122-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 606045 (gene) , 218330 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: 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, Lapponian Herder .

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
IFT122 intraflagellar transport 122 Canis lupus familiaris 20 NC_051824.1 (5745833..5673817) IFT122 Homologene, Ensembl, NCBI gene

Variants

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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
1301 Lapponian Herder Progressive retinal atrophy IFT122 missense Naturally occurring variant CanFam3.1 20 g.5648046C>T c.3176G>A p.(R1059H) Protein and CDS positions based on XP_533734.2 and XM_533734.6 2021 33606121

Reference


2021 Kaukonen, M., Pettinen, I.T., Wickström, K., Arumilli, M., Donner, J., Juhola, I.J., Holopainen, S., Turunen, J.A., Yoshihara, M., Kere, J., Lohi, H. :
A missense variant in IFT122 associated with a canine model of retinitis pigmentosa. Hum Genet 140:1569-1579, 2021. Pubmed reference: 33606121. DOI: 10.1007/s00439-021-02266-3.

Edit History


  • Created by Imke Tammen2 on 08 Apr 2021
  • Changed by Imke Tammen2 on 08 Apr 2021