RDH12 Mutations Cause a Severe Retinal Degeneration With Relatively Spared Rod Function.

Area of Science:

• Ophthalmology
• Genetics
• Retinal Diseases

Background:

• Inherited retinal degenerations (IRDs) encompass a group of genetic disorders affecting photoreceptor and retinal pigment epithelium function.
• Mutations in the retinol dehydrogenase 12 (RDH12) gene are a known cause of IRD, but the specific retinal phenotype in pediatric patients requires detailed characterization.

Purpose of the Study:

• To delineate the detailed retinal phenotype in pediatric patients diagnosed with RDH12-associated inherited retinal degeneration (RDH12-IRD).
• To correlate genotype with observed retinal abnormalities and functional deficits.

Main Methods:

• Ophthalmic examination and advanced imaging (SD-OCT, fundus autofluorescence) were performed on 21 patients from 14 families.
• Functional assessments included visual acuity, visual fields (Goldmann perimetry), electroretinography, and psychophysical testing (FST, pupillometry).

Main Results:

• Patients exhibited a wide range of visual acuity, from 20/40 to light perception.
• Key findings included parafoveal depigmentation, atrophic maculopathies, midperipheral pigment migration, foveal thinning, and reduced outer nuclear layer (ONL) and photoreceptor outer segment (POS) signals.
• Visual field testing revealed limited central islands of vision, and electroretinograms showed severely reduced or undetectable responses.

Conclusions:

• RDH12-IRD presents as an early-onset, retina-wide disease with severe central retinal abnormalities, resembling an early-onset cone-rod dystrophy.
• The presence of detectable ONL in the pericentral and peripapillary retina, despite severely abnormal POS, suggests these areas as potential targets for gene therapy interventions.