A novel homozygous nonsense variant in CABP4 causing stationary cone/rod synaptic dysfunction

Area of Science:

• Ophthalmology
• Genetics
• Neuroscience

Background:

• Congenital stationary night blindness (CSNB) is a group of inherited retinal diseases.
• Variants in the CABP4 gene have been linked to CSNB and synaptic diseases of photoreceptors.
• The full spectrum of CABP4-associated phenotypes requires further elucidation.

Observation:

• A patient presented with lifelong, non-progressive reduced visual acuity, photophobia, and impaired color vision, but notably lacked nyctalopia.
• Ocular examinations revealed hyperopia, nystagmus, and significantly reduced rod and cone responses on electroretinography.
• Targeted genetic analysis identified a novel homozygous nonsense variant (c.181C>T, p.Gln61*) in the CABP4 gene.

Findings:

• The identified homozygous CABP4 variant is associated with stationary cone and rod dysfunction.
• This variant leads to a distinct phenotype characterized by decreased visual acuity, color vision deficits, and photophobia.
• The clinical presentation differs from typical CSNB, suggesting a broader spectrum of CABP4-related retinal dysfunction.

Implications:

• This study expands the known genotype-phenotype correlations for CABP4.
• The findings highlight CABP4-related disorders as a form of retinal synaptic disease affecting both rods and cones.
• Further research into CABP4 function may reveal new therapeutic targets for inherited retinal diseases.