[Genotype-Phenotype Correlations in Patients with CRB1 Mutations].

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• CRB1 gene mutations are linked to early-onset severe retinal dystrophy (EOSRD) and various rod-cone dystrophies.
• This study investigates the clinical spectrum of CRB1-related retinal disorders in individuals up to 20 years of age.

Observation:

• Eight patients (3 months to 20 years) underwent comprehensive ophthalmological evaluations.
• Methods included visual acuity testing, color vision, funduscopy, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), electroretinography (ffERG), and visual field testing.
• SD-OCT data underwent automated and manual retinal layer segmentation using DIOCTA software.

Findings:

• Patients with null CRB1 mutations showed severe vision loss from infancy (BCVA ≤0.04).
• A homozygous missense mutation resulted in BCVA of 0.05 by age 6.
• Hypomorphic missense mutations were associated with better visual function (BCVA up to 0.5 at age 20).
• ffERG was subthreshold in most patients, with severely restricted visual fields.
• SD-OCT revealed reduced photoreceptor layers and increased inner nuclear layer thickness; A-Scan analysis indicated better retinal stratification preservation in missense mutation carriers.

Implications:

• CRB1 mutations typically cause severe, early-onset visual impairment.
• Missense mutations with residual CRB1 function correlate with a moderately expressed phenotype.
• Progressive visual field constriction occurs within the first decade of life.
• Reduced retinal stratification signifies compromised structural integrity in CRB1-related retinal degeneration.