Categories: Vision / eye phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 615004 (gene) , 615058 (trait)

Links to MONDO diseases:

• MONDO:0014026: congenital stationary night blindness 1F

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 name: Congenital stationary night blindness

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"

Miyadera et al. (2022) and Takahashi et al. (2023) report extended functional rescue following subretinal gene therapy.

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: