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

Yuquan Wen, Kirsten G. Locke, Martin Klein, Sara J. Bowne, Lori S. Sullivan, Joseph Ray, Stephen P. Daiger, David G. Birch, Dianna K. Hughbanks-Wheaton

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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, spectraldomain 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. Spectraldomain 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.

Original languageEnglish (US)
Pages (from-to)1475-1482
Number of pages8
JournalArchives of Ophthalmology
Volume129
Issue number11
DOIs
StatePublished - Nov 2011
Externally publishedYes

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Retinitis Pigmentosa
Visual Fields
Mutation
Vertebrate Photoreceptor Cells
Optical Coherence Tomography
Constriction
Visual Acuity
Retinal Rod Photoreceptor Cells
Phenotype
Electroretinography
Visual Field Tests
Photography
Proteins

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Phenotypic characterization of 3 families with autosomal dominant retinitis pigmentosa due to mutations in KLHL7. / Wen, Yuquan; Locke, Kirsten G.; Klein, Martin; Bowne, Sara J.; Sullivan, Lori S.; Ray, Joseph; Daiger, Stephen P.; Birch, David G.; Hughbanks-Wheaton, Dianna K.

In: Archives of Ophthalmology, Vol. 129, No. 11, 11.2011, p. 1475-1482.

Research output: Contribution to journalArticle

Wen, Y, Locke, KG, Klein, M, Bowne, SJ, Sullivan, LS, Ray, J, Daiger, SP, Birch, DG & Hughbanks-Wheaton, DK 2011, 'Phenotypic characterization of 3 families with autosomal dominant retinitis pigmentosa due to mutations in KLHL7', Archives of Ophthalmology, vol. 129, no. 11, pp. 1475-1482. https://doi.org/10.1001/archophthalmol.2011.307
Wen, Yuquan ; Locke, Kirsten G. ; Klein, Martin ; Bowne, Sara J. ; Sullivan, Lori S. ; Ray, Joseph ; Daiger, Stephen P. ; Birch, David G. ; Hughbanks-Wheaton, Dianna K. / Phenotypic characterization of 3 families with autosomal dominant retinitis pigmentosa due to mutations in KLHL7. In: Archives of Ophthalmology. 2011 ; Vol. 129, No. 11. pp. 1475-1482.
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abstract = "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, spectraldomain 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. Spectraldomain 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.",
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AU - Locke, Kirsten G.

AU - Klein, Martin

AU - Bowne, Sara J.

AU - Sullivan, Lori S.

AU - Ray, Joseph

AU - Daiger, Stephen P.

AU - Birch, David G.

AU - Hughbanks-Wheaton, Dianna K.

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N2 - 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, spectraldomain 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. Spectraldomain 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.

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