title: Cone structure in patients with usher syndrome type III and mutations in the Clarin 1 gene.
abstract: OBJECTIVE
  To study macular structure and function in patients with Usher syndrome type III (USH3) caused by mutations in the Clarin 1 gene (CLRN1).
  
  
  METHODS
  High-resolution macular images were obtained by adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in 3 patients with USH3 and were compared with those of age-similar control subjects. Vision function measures included best-corrected visual acuity, kinetic and static perimetry, and full-field electroretinography. Coding regions of the CLRN1 gene were sequenced.
  
  
  RESULTS
  CLRN1 mutations were present in all the patients; a 20-year-old man showed compound heterozygous mutations (p.N48K and p.S188X), and 2 unrelated women aged 25 and 32 years had homozygous mutations (p.N48K). Best-corrected visual acuity ranged from 20/16 to 20/40, with scotomas beginning at 3° eccentricity. The inner segment-outer segment junction or the inner segment ellipsoid band was disrupted within 1° to 4° of the fovea, and the foveal inner and outer segment layers were significantly thinner than normal. Cones near the fovea in patients 1 and 2 showed normal spacing, and the preserved region ended abruptly. Retinal pigment epithelial cells were visible in patient 3 where cones were lost.
  
  
  CONCLUSIONS
  Cones were observed centrally but not in regions with scotomas, and retinal pigment epithelial cells were visible in regions without cones in patients with CLRN1 mutations. High-resolution measures of retinal structure demonstrate patterns of cone loss associated with CLRN1 mutations.
  
  
  CONCLUSIONS
  These findings provide insight into the effect of CLRN1 mutations on macular cone structure, which has implications for the development of treatments for USH3.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00254605.
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, San Francisco, CA 94143-0730, USA.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Ratnam
authors.forename: Hanna
authors.initials: H
authors.lastname: Västinsalo
authors.forename: Austin
authors.initials: A
authors.lastname: Roorda
authors.forename: Eeva-Marja K
authors.initials: EM
authors.lastname: Sankila
authors.forename: Jacque L
authors.initials: JL
authors.lastname: Duncan
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D009887:Ophthalmoscopy; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012164:Retinal Diseases / Q000175:diagnosis* / Q000235:genetics; D055213:Retinal Pigment Epithelium / Q000473:pathology; D012607:Scotoma / Q000473:pathology; D041623:Tomography, Optical Coherence; D052245:Usher Syndromes / Q000175:diagnosis* / Q000235:genetics; D014792:Visual Acuity / Q000502:physiology; D058609:Visual Field Tests; D014794:Visual Fields / Q000502:physiology; D055815:Young Adult
chemical_list: C437067:CLRN1 protein, human; D008565:Membrane Proteins