Phenotypic Characterization of 3 Families With Autosomal Dominant Retinitis Pigmentosa Due to Mutations in KLHL7 | Genetics and Genomics | JAMA Ophthalmology | JAMA Network
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Ophthalmic Molecular Genetics
Nov 2011

Phenotypic Characterization of 3 Families With Autosomal Dominant Retinitis Pigmentosa Due to Mutations in KLHL7

Author Affiliations

Author Affiliations: Retina Foundation of the Southwest (Drs Wen, Birch, and Hughbanks-Wheaton, Ms Locke, and Mr Klein) and Department of Ophthalmology, The University of Texas Southwestern Medical Center (Drs Birch and Hughbanks-Wheaton), Dallas, and Human Genetics Center, School of Public Health, and Department of Ophthalmology and Visual Science, The University of Texas, Houston (Drs Bowne, Sullivan, Ray, and Daiger).

Arch Ophthalmol. 2011;129(11):1475-1482. doi:10.1001/archophthalmol.2011.307

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.