title: Clinical course of cone dystrophy caused by mutations in the RPGR gene.
abstract: BACKGROUND
  Mutations in the RPGR gene predominantly cause rod photoreceptor disorders with a large variability in clinical course. In this report, we describe two families with mutations in this gene and cone involvement.
  
  
  METHODS
  We investigated an X-linked cone dystrophy family (1) with 25 affected males, 25 female carriers, and 21 non-carriers, as well as a small family (2) with one affected and one unaffected male. The RPGR gene was analyzed by direct sequencing. All medical records were evaluated, and all available data on visual acuity, color vision testing, ophthalmoscopy, fundus photography, fundus autofluorescence, Goldmann perimetry, SD-OCT, dark adaptation, and full-field electroretinography (ERG) were registered. Cumulative risks of visual loss were studied with Kaplan-Meier product-limit survival analysis.
  
  
  RESULTS
  Both families had a frameshift mutation in ORF15 of the RPGR gene; family 1 had p.Ser1107ValfsX4, and family 2 had p.His1100GlnfsX10. Mean follow up was 13 years (SD 10). Virtually all affected males showed reduced photopic and normal scotopic responses on ERG. Fifty percent of the patients had a visual acuity of <0.5 at age 35 years (SE 2.2), and 75% of the patients was legally blind at age 60 years (SE 2.3). Female carriers showed no signs of ocular involvement.
  
  
  CONCLUSIONS
  This report describes the clinical course and visual prognosis in two families with cone dystrophy due to RPGR mutations in the 3' terminal region of ORF15. Remarkable features were the consistent, late-onset phenotype, the severe visual outcome, and the non-expression in female carriers. Expression of RPGR mutations in this particular region appears to be relatively homogeneous and predisposed to cones.
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, PO Box 2040, 3000, CA, Rotterdam, The Netherlands.
authors.forename: Alberta A H J
authors.initials: AA
authors.lastname: Thiadens
authors.forename: Gyan G
authors.initials: GG
authors.lastname: Soerjoesing
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Florijn
authors.forename: A G
authors.initials: AG
authors.lastname: Tjiam
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.forename: L Ingeborgh
authors.initials: LI
authors.lastname: van den Born
authors.forename: Frans C
authors.initials: FC
authors.lastname: Riemslag
authors.forename: Arthur A B
authors.initials: AA
authors.lastname: Bergen
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
mesh_terms: D000328:Adult; D004247:DNA / Q000235:genetics*; D003623:Dark Adaptation / Q000502:physiology*; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011379:Prognosis; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D005136:Eye Proteins; C099929:RPGR protein, human; D004247:DNA