A homogenous frameshift mutation in LRAT causes retinitis punctata albescens
| Autor: | Karin W. Littink, Frans C. C. Riemslag, Linda Visser, Mary J. van Schooneveld, Anneke I. den Hollander, Maria M. van Genderen, L. Ingeborgh van den Born, Jan E.E. Keunen, Bjorn Bakker, Marijke N. Zonneveld, Frans P.M. Cremers |
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| Přispěvatelé: | Netherlands Institute for Neuroscience (NIN), AII - Amsterdam institute for Infection and Immunity, Ophthalmology |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Candidate gene medicine.medical_specialty Genetics and epigenetic pathways of disease [NCMLS 6] Adolescent genetic structures DNA Mutational Analysis Visual Acuity Fundus (eye) Compound heterozygosity Polymerase Chain Reaction Polymorphism Single Nucleotide Retina Frameshift mutation Young Adult Cone dystrophy Retinal Diseases Ophthalmology Evaluation of complex medical interventions Genomic disorders and inherited multi-system disorders [NCEBP 2] medicine Electroretinography Humans Fluorescein Angiography Child Frameshift Mutation Aged Genetics medicine.diagnostic_test business.industry Homozygote Fundus photography Middle Aged medicine.disease Disease gene identification Alcohol Oxidoreductases Visual Field Tests Visual Fields business Genetics and epigenetic pathways of disease Genomic disorders and inherited multi-system disorders [NCMLS 6] Carrier Proteins Acyltransferases Tomography Optical Coherence Retinopathy |
| Zdroj: | Ophthalmology, 119, 1899-1906. Elsevier B.V. Ophthalmology, 119(9), 1899-1906. Elsevier Inc. Ophthalmology, 119, 9, pp. 1899-906 Ophthalmology, 119, 1899-906 |
| ISSN: | 0161-6420 |
| Popis: | Purpose: To determine the genetic defect and to describe the clinical characteristics in patients with retinitis punctata albescens (RPA) and fundus albipunctatus (FAP). Design: Case series/observational study. Participants: We included 13 patients affected by RPA or FAP. Methods: Thirteen patients were collected from 8 families with a retinal dystrophy characterized by tiny, yellow-white dots on funduscopy, typical for FAP or RPA. All patients underwent full ophthalmologic examinations, including visual field assessment. Fundus photography, and electroretinography were performed in 12 patients, and optical coherence tomography and fundus autofluorescence were performed in 4 patients. DNA samples of all patients were screened for mutations in RLBP1 and for mutations in RDH5 in patients who did not carry mutations in RLBP1. DNA samples of 2 sibling pairs of nonconsanguineous families who carried mutations neither in RLBP1 nor in RDH5 were analyzed by genome-wide homozygosity mapping. Sequence analysis was performed of LRAT, a candidate gene in a shared homozygous region. Main Outcome Measures: We assessed DNA sequence variants, best-corrected visual acuity, fundus appearance, visual field measurements, electroretinogram responses, optical coherence tomography, and fundus autofluorescence. Results: A homozygous frameshift mutation was identified in LRAT in 4 patients with RPA. Mutations in RLBP1 were identified in 7 patients with RPA and in 1 patient with FAP and cone dystrophy. One patient had compound heterozygous mutations in RDH5 and suffered from FAP with mild maculopathy. Conclusions: A genetic defect was identified in LRAT as a novel cause of RPA. LRAT is therefore the fourth gene involved in the visual cycle that may cause a white-dot retinopathy. We also revealed that mutations in RLBP1 may lead to FAP with cone dystrophy. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012; 119: 1899-1906 (C) 2012 by the American Academy of Ophthalmology |
| Databáze: | OpenAIRE |
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