title: Lack of Interphotoreceptor Retinoid Binding Protein Caused by Homozygous Mutation of RBP3 Is Associated With High Myopia and Retinal Dystrophy.
abstract: OBJECTIVE
  We present a detailed clinical and molecular study of four patients from two consanguineous families with a similar childhood-onset retinal dystrophy resulting from novel homozygous nonsense mutations in RBP3.
  
  
  METHODS
  Four children with mutations in RBP3 encoding interphotoreceptor binding protein (IRBP) were ascertained by whole exome sequencing and subsequent direct Sanger sequencing. Detailed phenotyping was performed, including full clinical evaluation, electroretinography, fundus photography, fundus autofluorescence (FAF) imaging, and spectral-domain optical coherence tomography (OCT).
  
  
  RESULTS
  Two novel homozygous nonsense mutations (c.1530T>A;p.Y510* and c.3454G>T;p.E1152*) in RBP3 were identified in four patients from two families. All four patients had a similar, unusual retinal dystrophy characterized by childhood onset high myopia, generalized rod and cone dysfunction, and an unremarkable fundus appearance. The FAF imaging showed multiple paracentral foci of low autofluorescence in one patient and patchy increased FAF in the region of the vascular arcades in another. The OCT showed loss of outer retinal bands over peripheral macular areas in all 4 cases.
  
  
  CONCLUSIONS
  To our knowledge, this report is the first to describe the retinal dystrophy in children caused by homozygous nonsense RBP3 mutations, highlighting the requirement for IRBP in normal eye development and visual function. Longitudinal study will reveal if the four children reported here will progress to a more typical retinitis pigmentosa phenotype described previously in adults with RBP3 mutations. The RBP3-related disease should be considered in children with high myopia and retinal dystrophy, particularly when there are no significant fundus changes.
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom 2Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Gavin
authors.initials: G
authors.lastname: Arno
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom 2Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hull
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom 2Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Robson
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom 2Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Graham E
authors.initials: GE
authors.lastname: Holder
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cheetham
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom 2Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
authors.affiliation: University College London Genetics Institute, London, United Kingdom.
authors.forename: Vincent
authors.initials: V
authors.lastname: Plagnol
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom 2Moorfields Eye Hospital, London, United Kingdom 4Ophthalmology Department, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom 5Department of Ophthalmology, University of Cali.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
mesh_terms: D000293:Adolescent; D002648:Child; D018389:Codon, Nonsense; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D006720:Homozygote; D006801:Humans; D008297:Male; D009216:Myopia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D012029:Refraction, Ocular; D012160:Retina / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D041623:Tomography, Optical Coherence; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D018389:Codon, Nonsense; D004247:DNA; D005136:Eye Proteins; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial