title: Clinical characteristics of early retinal disease due to CDHR1 mutation.
abstract: OBJECTIVE
  To describe the early clinical and electrophysiological features of cone-rod dystrophy due to a mutation of cadherin-related family member 1 (CDHR1).
  
  
  METHODS
  Three affected siblings from a consanguineous family were ascertained. The clinical data included retinal examination, Goldmann visual fields, fundus autofluorescence imaging, optical coherence tomography (OCT), and pattern and full-field electroretinograms. Exome sequencing was performed in two siblings.
  
  
  RESULTS
  The three siblings presented at age 24, 18, and 16 years, respectively. Their main symptoms were blurred central vision, dyschromatopsia, and photoaversion. All were myopic with best-corrected visual acuities of 20/60, 20/60, and 20/40, respectively. Fundoscopy revealed a range of macular appearances from mild retinal pigment epithelial changes to symmetric, subfoveal pigmented lesions. Fundus autofluorescence imaging and OCT revealed evidence of mild structural abnormalities in the two older siblings. Electroretinography findings in all three patients indicated severe generalized cone-rod dysfunction. Mutational screening in the three siblings showed them to be homozygous for a previously reported frame-shifting mutation in exon 13 of CDHR1, c.1463delG, p.G488fs.
  
  
  CONCLUSIONS
  The initial clinical signs in this specific retinopathy may be relatively subtle despite a significant functional deficit, with unusual, bilateral, subfoveal pigmented lesions in one 16-year-old patient. Lack of CDHR1 in the human retina causes symptoms related to cone photoreceptor dysfunction in the first instance. A near-normal retinal structure, at least in the first two decades, suggests that CDHR1-related retinopathy may be a good candidate for gene replacement or other novel stabilizing treatments.
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, UK ; Moorfields Eye Hospital, London, UK ; Ophthalmology Department, King Abdulaziz University Hospital, Riyadh, Saudi Arabia.
authors.forename: Rola
authors.initials: R
authors.lastname: Ba-Abbad
authors.forename: Panagiotis I
authors.initials: PI
authors.lastname: Sergouniotis
authors.forename: Vincent
authors.initials: V
authors.lastname: Plagnol
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Robson
authors.forename: Michel
authors.initials: M
authors.lastname: Michaelides
authors.forename: Graham E
authors.initials: GE
authors.lastname: Holder
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics*; D055724:Electrophysiological Phenomena; D004596:Electroretinography; D005260:Female; D005654:Fundus Oculi; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012164:Retinal Diseases / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D014794:Visual Fields; D055815:Young Adult
chemical_list: C442481:CDHR1 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D009419:Nerve Tissue Proteins