OMIA:001486-9615 : Night blindness, congenital stationary, LRIT3-related in Canis lupus familiaris
Categories: Vision / eye phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 615004 (gene) , 615058 (trait)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2019
Species-specific symbol: CSNB
Species-specific description: Kondo et al. (2015) reported "a naturally occurring disease in the beagle dog that is a model for autosomal recessive [complete Congenital Stationary Night Blindness] cCSNB in man"
Inheritance: Kondo et al. (2015): "o define the inheritance pattern for the disease, a colony of beagle dogs with CSNB was developed from 3 founder animals (F5858, M4 and M6233), and expanded by outcross, backcross and intercross to produce affected (n = 24) and obligate carrier (n = 22) dogs . . . . Dominant inheritance was excluded as the progeny (n = 11), both male and female, were phenotypically normal when affected dogs were outcrossed to unrelated normal dogs (expected = 5-6/11 dogs affected; observed = 0/11). When the progeny was used in backcrosses to affected animals, they produced affected and non-affected offspring in approximately 1:1 ratio as expected for an autosomal recessive disease. X-linked inheritance was ruled out as both sexes were affected in the pedigree. Eight of the nineteen offspring produced as a result of mating between obligate carrier and affected dogs had the CSNB phenotype. Mating between affected dogs resulted in pups all of which had the CSNB phenotype. These results are consistent with autosomal recessive mode of inheritance."
Mapping: Das et al. (2019): "A genome-wide association study using 12 cases and 11 controls from a research colony determined a 4.6 Mb locus on canine chromosome 32"
Molecular basis: Sequencing of candidate genes by Kondo et al. (2015) failed to reveal any likely causal mutations.
Das et al. (2019): "whole-genome sequencing identified a 1 bp deletion in LRIT3 segregating with CSNB [in the same Beagle colony as reported by Kondo et al. (2015)]. The canine mutant LRIT3 gives rise to a truncated protein with unaltered subcellular expression in vitro"
Clinical features: Kondo et al. (2015) reported "Affected dogs had normal retinas on clinical examination, but showed no detectable rod responses. They had “negative-type” mixed rod and cone responses in full-field ERGs. Their photopic long-flash ERGs had normal OFF-responses associated with severely reduced ON-responses. The phenotype is similar to the Schubert-Bornschein form of complete CSNB in humans."
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|LRIT3||leucine-rich repeat, immunoglobulin-like and transmembrane domains 3||Canis lupus familiaris||32||NC_051836.1 (30245558..30265027)||LRIT3||Homologene, Ensembl , NCBI gene|
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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|
|1260||Beagle||Night blindness, congenital stationary, LRIT3-related||LRIT3||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||32||g.30038863del||c.763del||p.(K245Nfs*5)||c.763delG||2019||31578364|
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2022||Miyadera, K., Santana, E., Roszak, K., Iffrig, S., Visel, M., Iwabe, S., Boyd, R.F., Bartoe, J.T., Sato, Y., Gray, A., Ripolles-Garcia, A., Dufour, V.L., Byrne, L.C., Flannery, J.G., Beltran, W.A., Aguirre, G.D. :|
|Targeting ON-bipolar cells by AAV gene therapy stably reverses LRIT3-congenital stationary night blindness. Proc Natl Acad Sci U S A 119:e2117038119, 2022. Pubmed reference: 35316139 . DOI: 10.1073/pnas.2117038119.|
|2020||Switonski, M. :|
|Impact of gene therapy for canine monogenic diseases on the progress of preclinical studies. J Appl Genet 61:179-186, 2020. Pubmed reference: 32189222 . DOI: 10.1007/s13353-020-00554-8.|
|2019||Das, R.G., Becker, D., Jagannathan, V., Goldstein, O., Santana, E., Carlin, K., Sudharsan, R., Leeb, T., Nishizawa, Y., Kondo, M., Aguirre, G.D., Miyadera, K. :|
|Genome-wide association study and whole-genome sequencing identify a deletion in LRIT3 associated with canine congenital stationary night blindness. Sci Rep 9:14166, 2019. Pubmed reference: 31578364 . DOI: 10.1038/s41598-019-50573-7.|
|2018||Oh, A., Loew, E.R., Foster, M.L., Davidson, M.G., English, R.V., Gervais, K.J., Herring, I.P., Mowat, F.M. :|
|Phenotypic characterization of complete CSNB in the inbred research beagle: how common is CSNB in research and companion dogs? Doc Ophthalmol :, 2018. Pubmed reference: 30051304 . DOI: 10.1007/s10633-018-9653-y.|
|2015||Kondo, M., Das, G., Imai, R., Santana, E., Nakashita, T., Imawaka, M., Ueda, K., Ohtsuka, H., Sakai, K., Aihara, T., Kato, K., Sugimoto, M., Ueno, S., Nishizawa, Y., Aguirre, G.D., Miyadera, K. :|
|A naturally occurring canine model of autosomal recessive congenital stationary night blindness. PLoS One 10:e0137072, 2015. Pubmed reference: 26368928 . DOI: 10.1371/journal.pone.0137072.|
- Created by Frank Nicholas on 20 Jan 2016
- Changed by Frank Nicholas on 20 Jan 2016
- Changed by Frank Nicholas on 30 Oct 2020