PMID- 30193310 OWN - NLM STAT- MEDLINE DCOM- 20190419 LR - 20201209 IS - 1552-5783 (Electronic) IS - 0146-0404 (Linking) VI - 59 IP - 11 DP - 2018 Sep 4 TI - Clinical Characterization of 66 Patients With Congenital Retinal Disease Due to the Deep-Intronic c.2991+1655A>G Mutation in CEP290. PG - 4384-4391 LID - 10.1167/iovs.18-24817 [doi] AB - PURPOSE: To describe the phenotypic spectrum of retinal disease caused by the c.2991+1655A>G mutation in CEP290 and to compare disease severity between homozygous and compound heterozygous patients. METHODS: Medical records were reviewed for best-corrected visual acuity (BCVA), age of onset, fundoscopy descriptions. Foveal outer nuclear layer (ONL) and ellipsoid zone (EZ) presence was assessed using spectral-domain optical coherence tomography (SD-OCT). Differences between compound heterozygous and homozygous patients were analyzed based on visual performance and visual development. RESULTS: A total of 66 patients were included. The majority of patients had either light perception or no light perception. In the remaining group of 14 patients, median BCVA was 20/195 Snellen (0.99 LogMAR; range 0.12-1.90) for the right eye, and 20/148 Snellen (0.87 LogMAR; range 0.22-1.90) for the left. Homozygous patients tended to be more likely to develop light perception compared to more severely affected compound heterozygous patients (P = 0.080) and are more likely to improve from no light perception to light perception (P = 0.022) before the age of 6 years. OCT data were available in 12 patients, 11 of whom had retained foveal ONL and EZ integrity up to 48 years (median 23 years) of age. CONCLUSIONS: Homozygous patients seem less severely affected compared to their compound-heterozygous peers. Improvement of visual function may occur in the early years of life, suggesting a time window for therapeutic intervention up to the approximate age of 17 years. This period may be extended by an intact foveal ONL and EZ on OCT. FAU - Valkenburg, Dyon AU - Valkenburg D AD - Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands. AD - Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Cognitive Neuroscience Department, Nijmegen, The Netherlands. FAU - van Cauwenbergh, Caroline AU - van Cauwenbergh C AD - Department of Ophthalmology, Ghent University and Ghent University Hospital, Ghent, Belgium. AD - Center for Medical Genetics Ghent, Ghent University and Ghent University Hospital, Ghent, Belgium. FAU - Lorenz, Birgit AU - Lorenz B AD - Department of Ophthalmology, Giessen University Medical Center, Giessen, Germany. FAU - van Genderen, Mies M AU - van Genderen MM AD - Bartimeus Institute for the Visually Impaired, Zeist and Doorn, The Netherlands. FAU - Bertelsen, Mette AU - Bertelsen M AD - Department of Ophthalmology, Righospitalet, Glostrup, Denmark. AD - Department of Clinical Genetics, Righospitalet, Copenhagen, Denmark. FAU - Pott, Jan-Willem R AU - Pott JR AD - Department of Ophthalmology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. FAU - Coppieters, Frauke AU - Coppieters F AD - Center for Medical Genetics Ghent, Ghent University and Ghent University Hospital, Ghent, Belgium. FAU - de Zaeytijd, Julie AU - de Zaeytijd J AD - Department of Ophthalmology, Ghent University and Ghent University Hospital, Ghent, Belgium. FAU - Thiadens, Alberta A H J AU - Thiadens AAHJ AD - Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands. FAU - Klaver, Caroline C W AU - Klaver CCW AD - Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands. AD - Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands. AD - Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. FAU - Kroes, Hester Y AU - Kroes HY AD - Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - van Schooneveld, Mary J AU - van Schooneveld MJ AD - Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands. FAU - Preising, Markus AU - Preising M AD - Department of Ophthalmology, Giessen University Medical Center, Giessen, Germany. FAU - Hoyng, Carel B AU - Hoyng CB AD - Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands. AD - Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Cognitive Neuroscience Department, Nijmegen, The Netherlands. FAU - Leroy, Bart P AU - Leroy BP AD - Department of Ophthalmology, Ghent University and Ghent University Hospital, Ghent, Belgium. AD - Center for Medical Genetics Ghent, Ghent University and Ghent University Hospital, Ghent, Belgium. AD - Division of Ophthalmology & Center for Cellular & Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States. FAU - van den Born, L Ingeborgh AU - van den Born LI AD - The Rotterdam Eye Hospital and Rotterdam Ophthalmic Institute, Rotterdam, The Netherlands. FAU - Collin, Rob W J AU - Collin RWJ AD - Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Cognitive Neuroscience Department, Nijmegen, The Netherlands. AD - Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Antigens, Neoplasm) RN - 0 (Cell Cycle Proteins) RN - 0 (Cep290 protein, human) RN - 0 (Cytoskeletal Proteins) RN - 0 (Neoplasm Proteins) SB - IM MH - Adolescent MH - Adult MH - Antigens, Neoplasm/*genetics MH - Cell Cycle Proteins MH - Child MH - Child, Preschool MH - Cytoskeletal Proteins MH - Electroretinography MH - Female MH - Follow-Up Studies MH - Gene Amplification MH - High-Throughput Nucleotide Sequencing MH - Humans MH - Infant MH - Introns/*genetics MH - Leber Congenital Amaurosis/*diagnosis/*genetics/physiopathology MH - Male MH - Middle Aged MH - *Mutation MH - Neoplasm Proteins/*genetics MH - Polymerase Chain Reaction MH - Retina/diagnostic imaging/physiopathology MH - Retrospective Studies MH - Tomography, Optical Coherence MH - Visual Acuity/physiology MH - Young Adult EDAT- 2018/09/08 06:00 MHDA- 2019/04/20 06:00 CRDT- 2018/09/08 06:00 PHST- 2018/09/08 06:00 [entrez] PHST- 2018/09/08 06:00 [pubmed] PHST- 2019/04/20 06:00 [medline] AID - 2701826 [pii] AID - 10.1167/iovs.18-24817 [doi] PST - ppublish SO - Invest Ophthalmol Vis Sci. 2018 Sep 4;59(11):4384-4391. doi: 10.1167/iovs.18-24817.