Phenotypic characterization of 3 families with autosomal dominant retinitis pigmentosa due to mutations in KLHL7.

OBJECTIVE: To characterize the visual phenotype caused by mutations in the BTB-Kelch protein, KLHL7, responsible for the RP42 form of autosomal dominant retinitis pigmentosa (RP).

METHODS: Comprehensive ophthalmic testing included visual acuity, static visual field, kinetic visual field, dark adaptometry, full-field electroretinography, spectral-domain optical coherence tomography, and fundus photography. Longitudinal visual function data (range, 15-27 years) were available for some of the affected individuals.

RESULTS: We report a phenotypic assessment of 3 unrelated families, each harboring different KLHL7 mutations (c.458C>T, c.449G>A, and c.457G>A). The fundi showed classic signs of RP. Best-corrected visual acuity was 20/50 or better in at least one eye up to age 65 years. Static and kinetic visual fields showed concentric constriction to central 10° to 20° by age 65 years; 2 patients with Goldmann perimetry exhibited bilateral visual field retention in the far periphery. Both rod and cone full-field electroretinographic amplitudes were substantially lower than normal, with a decline rate of 3% per year in cone 31-Hz flicker response. Rod and cone activation and inactivation variables were abnormal. Spectral-domain optical coherence tomography indicated retention of foveal inner segment-outer segment junction through age 65 years.

CONCLUSIONS: Mutations in KLHL7 are associated with a late-onset form of autosomal dominant retinal degeneration that preferentially affects the rod photoreceptors. Full-field electroretinographic findings, including recovery kinetics, are consistent with those observed in other forms of autosomal dominant RP.

CLINICAL RELEVANCE: The phenotypes are similar among patients with 3 types of KLHL7 mutations (c.458C>T, c.449G>A, and c.457G>A). Strong retention of foveal function and bilateral concentric constriction of visual fields with far periphery sparing may guide mutation screening in autosomal dominant RP.