OMIA 001486-9615 : Night blindness, congenital stationary, LRIT3-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 615004

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."

Breed: Beagle.

Associated gene:

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

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Beagle Night blindness, congenital stationary, LRIT3-related LRIT3 deletion, small (<=20) CanFam3.1 32 g.30,038,862_30,038,863delG c.762_763delG p.(249*) 2019 31578364

References


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.
2020 Switonski, M. :
Impact of gene therapy for canine monogenic diseases on the progress of preclinical studies. J Appl Genet :, 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.

Edit History


  • Created by Frank Nicholas on 20 Jan 2016
  • Changed by Frank Nicholas on 20 Jan 2016
  • Changed by Frank Nicholas on 30 Oct 2020