title: Phenotypic characterization of 3 families with autosomal dominant retinitis pigmentosa due to mutations in KLHL7.
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, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Retina Foundation of the Southwest, Dallas, TX 75231, USA. ywen@retinafoundation.org
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wen
authors.forename: Kirsten G
authors.initials: KG
authors.lastname: Locke
authors.forename: Martin
authors.initials: M
authors.lastname: Klein
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Bowne
authors.forename: Lori S
authors.initials: LS
authors.lastname: Sullivan
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Ray
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Daiger
authors.forename: David G
authors.initials: DG
authors.lastname: Birch
authors.forename: Dianna K
authors.initials: DK
authors.lastname: Hughbanks-Wheaton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001324:Autoantigens / Q000235:genetics*; D003623:Dark Adaptation; D004596:Electroretinography; D005260:Female; D005500:Follow-Up Studies; D005654:Fundus Oculi; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D016133:Polymerase Chain Reaction; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology; D041623:Tomography, Optical Coherence; D014786:Vision Disorders / Q000235:genetics* / Q000503:physiopathology; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology
chemical_list: D001324:Autoantigens; C505353:KLHL7 protein, human
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