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Mutations in RD3 are associated with an extremely rare and severe form of early onset retinal dystrophy

Item Type:Article
Title:Mutations in RD3 are associated with an extremely rare and severe form of early onset retinal dystrophy
Creators Name:Preising, M.N. and Hausotter-Will, N. and Solbach, M.C. and Friedburg, C. and Rueschendorf, F. and Lorenz, B.
Abstract:Purpose: To identify the underlying mutation and describe the phenotype in a consanguineous Kurdish family with Leber's congenital amaurosis (LCA)/early onset severe retinal dystrophy (EOSRD). Methods: Members of the index family were followed up to 22 years by ophthalmological examinations, including best corrected visual acuity (BCVA), Goldmann visual field (GVF), two-color-threshold perimetry (2CTP) and Ganzfeld electroretinogram (ERG), fundus photographs, fundus autofluorescence (FAF), and optical coherence tomography (OCT). After excluding seven of nine known LCA/EOSRD genes in the index patient, linkage analysis was performed in the family using a microarray followed by microsatellite fine mapping and direct sequencing of candidate genes. RD3 was screened by direct sequencing of 85 independent patients with LCA/EOSRD presenting with a BCVA ≥ 1.0 LogMAR before the age of 2 years to assess the prevalence of RD3 mutations in LCA/EOSRD. Since RD3 and RetGC1 have a functional relation, study authors screened for a modifying effect of RD3 mutations in 17 independent patients with mutations in GUCY2D. Results: BCVA was severely reduced from the earliest examinations (as early as 3 months), never exceeding 1.3 LogMAR. The disease presented as cone-rod dystrophy with dystrophic changes in the macula and bone spicules in the periphery on progression. Linkage analysis narrowed the region of interest towards the LCA12 locus. Direct sequencing of RD3 revealed a homozygous nonsense mutation (c.180C > A) in all affected members tested. Screening of additional unrelated LCA/EOSRD patients revealed only polymorphisms in RD3. Conclusions: This is the second family reported so far with mutations in RD3. Mutations in RD3 are a very rare cause of LCA associated with an extremely severe form of retinal dystrophy.
Keywords:Consanguinity, Electroretinography, Eye Proteins, Infant, Leber Congenital Amaurosis, Nonsense Codon, Optical Coherence Tomography, Pedigree, Phenotype, Retinal Dystrophies, Single Nucleotide Polymorphism, Visual Acuity, Visual Field Tests, Visual Fields
Source:Investigative Ophthalmology & Visual Science
Publisher:Association for Research in Vision and Ophthalmology
Page Range:3463-3472
Date:8 June 2012
Official Publication:https://doi.org/10.1167/iovs.12-9519
PubMed:View item in PubMed

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