Test Detail

A form of late-onset progressive retinal atrophy (PRA) caused by a variant in the IFT122 gene, which encodes a protein of the intraflagellar transport complex IFT-A, essential for maintenance of the connecting cilium and photoreceptor function. It was first described in the Lapponian Herder and the same variant was subsequently identified in the related breed Finnish Lapphund, with a carrier frequency of around 12%. Causality in the Finnish Lapphund is still being elucidated, so interpretation of the test in this breed requires caution.

Affected breeds: Lapponian Herder and Finnish Lapphund. In the Finnish Lapphund the carrier frequency of the IFT122 variant was 12% (68/577). In the Lapponian Herder no large series with a reliable allele frequency have been published; consider 'limited data'. The variant has not been found in other breeds analysed.

- Test breeding stock of Lapponian Herder and Finnish Lapphund with the IFT122 c.3176G>A test before mating\n- In the Lapponian Herder, where causality is better established, do not mate two carriers: 25% risk of potentially affected homozygotes\n- In the Finnish Lapphund, manage the result with caution: avoid mating two carriers as a precaution, but remember that clinical causality in the breed is not confirmed and that a homozygote will not necessarily develop PRA\n- A carrier may be mated with a clear animal; offspring intended for breeding should be tested and the clear animal preferably selected, progressively replacing the carrier without narrowing the gene pool\n- Complement the genetic test with annual ophthalmological examination of breeding stock: a negative IFT122 result does not exclude other forms of PRA in the breed (PRCD, BEST1, and forms yet to be characterised)\n- In the case of PRA in a Finnish Lapphund without the PRCD variant, do not automatically attribute it to IFT122: consider the existence of other genetic causes yet to be identified

Differential diagnosis with other forms of PRA described in the Lapponian Herder and Finnish Lapphund (PRCD, cmr3 due to BEST1) and with PRA of non-genetic causes (chronic uveitis, glaucoma, toxins, nutritional vitamin E deficiency). ERG shows early rod involvement (initial night blindness). In the Finnish Lapphund, interpretation of the IFT122 test must be cautious: inform the owner that a homozygote will not necessarily develop PRA and that the genotype-phenotype relationship in the breed is under investigation. The identification of IFT122 as a new retinitis pigmentosa gene is of translational interest, as it opens the way to studying IFT122 in human patients with RP of unclear molecular cause.

1. Kaukonen M, Pettinen IT, Wickström K, Arumilli M, Donner J, Juhola IJ, Holopainen S, Turunen JA, Yoshihara M, Kere J, Lohi H (2021) A missense variant in IFT122 associated with a canine model of retinitis pigmentosa. Hum Genet 140:1569-1579. PMID: 33606121
2. OMIA:002320-9615. Retinal atrophy, progressive, IFT122-related in Canis lupus familiaris. https://omia.org/OMIA002320/9615/