title: Childhood cone-rod dystrophy with macular cystic degeneration from recessive CRB1 mutation.
abstract: OBJECTIVE
  To describe three siblings with childhood cone-rod dystrophy and macular cystic degeneration in a family with apparently variable phenotypes of CRB1-related recessive retinal dystrophy.
  
  
  METHODS
  Ophthalmologic examination (including electroretinography (ERG), ocular coherence tomography (OCT), and intravenous fluorescein angiography when possible) and homozygosity analysis guided candidate gene testing.
  
  
  RESULTS
  When the proband was evaluated at 7 years old for progressive visual loss, fundus exam was unremarkable (including no macular thickening clinically or by OCT) but ERG revealed cone-rod dysfunction with an electronegative waveform. Four years later repeat examination was significant for bilateral macular cystic degeneration and immediate family members were evaluated. Both the older sister (15 years old) and the younger brother (7 years old) had cone-rod dystrophy with macular cystic degeneration. Both the father (45 years old) and mother (35 years old) had had early adult-onset nyctalopia with later eventual loss of central vision; examination revealed dystrophic retinas with mostly peripheral clumped and/or nummular pigment and macular atrophy. ERG for both the older sister and younger brother confirmed cone-rod dysfunction (without an electronegative waveform) and was non-recordable for both the parents. Homozygosity analysis guided candidate gene analysis and confirmatory Sanger sequencing for the family uncovered a homozygous CRB1 mutation (c.80G > T [p.Cys27Phe]) in affected family members.
  
  
  CONCLUSIONS
  The phenotypic spectrum of recessive CRB1 mutation includes childhood cone-rod dystrophy with macular cystic degeneration and the associated ERG can be electronegative.
authors.affiliation: Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital , Riyadh , Saudi Arabia .
authors.forename: Arif O
authors.initials: AO
authors.lastname: Khan
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Aldahmesh
authors.forename: Leen
authors.initials: L
authors.lastname: Abu-Safieh
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003241:Consanguinity; D003560:Cysts / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012160:Retina / Q000502:physiology; D012164:Retinal Diseases / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D041623:Tomography, Optical Coherence
chemical_list: C448939:CRB1 protein, human; D005136:Eye Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins
keywords: CRB1; Cone-rod dystrophy; macular cystic degeneration; rod-cone dystrophy