title: Vitamin A deficiency due to bi-allelic mutation of RBP4: There's more to it than meets the eye.
abstract: Vitamin A deficiency is the leading cause of preventable blindness in children worldwide and results in a well-recognized ocular phenotype. Herein we describe a patient presenting to the eye clinic with a retinal dystrophy and ocular colobomata. This combination of clinical signs and consanguineous pedigree structure suggested a genetic basis for the disease, a hypothesis that was tested using whole genome sequencing. Bi-allelic mutations in RBP4 were identified (c.248+1G>A), consistent with a diagnosis of inherited vitamin A deficiency. We describe a constellation of signs that appear to be characteristic for this disease, increasing clinical awareness of this rare condition.
authors.affiliation: a University College London Institute of Ophthalmology , University College London , London , UK.|b Medical Retina Service , Moorfields Eye Hospital , London , UK.|c Department of Ophthalmology, Leeds Institute of Molecular Medicine , St. James' University Hospital , Leeds , UK.
authors.forename: Kamron N
authors.initials: KN
authors.lastname: Khan
authors.affiliation: d University Department of Medical Genetics , Cambridge Institute for Medical Research, Addenbrooke's Hospital , Cambridge , UK.
authors.forename: Keren
authors.initials: K
authors.lastname: Carss
authors.affiliation: d University Department of Medical Genetics , Cambridge Institute for Medical Research, Addenbrooke's Hospital , Cambridge , UK.
authors.forename: F Lucy
authors.initials: FL
authors.lastname: Raymond
authors.affiliation: b Medical Retina Service , Moorfields Eye Hospital , London , UK.
authors.forename: Farrah
authors.initials: F
authors.lastname: Islam
authors.affiliation: b Medical Retina Service , Moorfields Eye Hospital , London , UK.
authors.lastname: Nihr BioResource-Rare Diseases Consortium
authors.affiliation: a University College London Institute of Ophthalmology , University College London , London , UK.|b Medical Retina Service , Moorfields Eye Hospital , London , UK.|e Ophthalmology Department , University of California, San Francisco Medical School , San Francisco , California , USA.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
authors.affiliation: a University College London Institute of Ophthalmology , University College London , London , UK.|b Medical Retina Service , Moorfields Eye Hospital , London , UK.
authors.forename: Michel
authors.initials: M
authors.lastname: Michaelides
authors.affiliation: a University College London Institute of Ophthalmology , University College London , London , UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Arno
mesh_terms: D000328:Adult; D000483:Alleles; D003103:Coloboma / Q000097:blood / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D006801:Humans; D007498:Iris / Q000002:abnormalities*; D008850:Microphthalmos / Q000097:blood / Q000235:genetics*; D009154:Mutation; D012174:Retinitis Pigmentosa / Q000097:blood / Q000235:genetics*; D054839:Retinol-Binding Proteins, Plasma / Q000235:genetics*; D041623:Tomography, Optical Coherence; D014801:Vitamin A / Q000097:blood; D014802:Vitamin A Deficiency / Q000097:blood / Q000235:genetics*; D000073336:Whole Genome Sequencing
chemical_list: C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma; D014801:Vitamin A
keywords: Iris coloboma; RBP4; microphthalmia; serum retinol level; vitamin A deficiency; whole genome sequencing