Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature
| Autor: | Anthony T. Moore, Yann Nadjar, Miodrag Vojcic, Patrick Yu-Wai-Man, F. Lucy Raymond, James Acheson, Anthony G. Robson, Guy Lenaers, Mary M. Reilly, Neringa Jurkute, Andrew R. Webster, Jenny Higgs, Gavin Arno, Priya D. Shanmugarajah, Marios Hadjivassiliou, Valérie Touitou, Iain Horrocks, Roy Poh |
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| Přispěvatelé: | University College of London [London] (UCL), NHS Foundation Trust [London], The Royal Marsden, Royal Hallamshire Hospital, Liverpool Women's NHS Foundation Trust, Royal Victoria Infirmary, Newcastle upon Tyne, Royal Hospital for Sick Children, Glasgow, Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Ophtalmologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UCL, Institute of Neurology [London], University of Cambridge [UK] (CAM), Institute of Neurology, Queen Square, London, University of California (UC), HAL-SU, Gestionnaire, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), University of California, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Retinal degeneration Adult Male Adolescent Mutation Missense Visual Acuity Disease Retina syndromic optic neuropathy 03 medical and health sciences ferredoxin reductase Young Adult 0302 clinical medicine Atrophy Retinal Dystrophies Exome Sequencing medicine Genetics Electroretinography Missense mutation Humans retinal dystrophy Child Exome sequencing Retrospective Studies Whole genome sequencing [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology business.industry Haplotype medicine.disease 3. Good health Pedigree Ferredoxin-NADP Reductase 030104 developmental biology Phenotype FDXR iron accumulation Child Preschool Female business neurodegenerative disorder 030217 neurology & neurosurgery [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | Investigative Ophthalmology & Visual Science Investigative Ophthalmology & Visual Science, 2021, 62 (6), pp.2. ⟨10.1167/iovs.62.6.2⟩ Investigative Ophthalmology & Visual Science, Association for Research in Vision and Ophthalmology, 2021, 62 (6), pp.2. ⟨10.1167/iovs.62.6.2⟩ |
| ISSN: | 0146-0404 1552-5783 |
| DOI: | 10.1167/iovs.62.6.2⟩ |
| Popis: | Author(s): Jurkute, Neringa; Shanmugarajah, Priya D; Hadjivassiliou, Marios; Higgs, Jenny; Vojcic, Miodrag; Horrocks, Iain; Nadjar, Yann; Touitou, Valerie; Lenaers, Guy; Poh, Roy; Acheson, James; Robson, Anthony G; Raymond, F Lucy; Reilly, Mary M; Yu-Wai-Man, Patrick; Moore, Anthony T; Webster, Andrew R; Arno, Gavin; Genomics England Research Consortium | Abstract: PurposeThe purpose of this study was to report retinal dystrophy as a novel clinical feature and expand the ocular phenotype in patients harboring biallelic candidate FDXR variants.MethodsPatients carrying biallelic candidate FDXR variants were identified by whole genome sequencing (WGS) as part of the National Institute for Health Research BioResource rare-disease and the UK's 100,000 Genomes Project (100KGP) with an additional case identified by exome sequencing. Retrospective clinical data were collected from the medical records. Haplotype reconstruction was performed in families harboring the same missense variant.ResultsTen individuals from 8 unrelated families with biallelic candidate variants in FDXR were identified. In addition to bilateral optic atrophy and variable extra-ocular findings, 7 of 10 individuals manifested retinal dystrophy comprising dysfunction and degeneration of both rod and cone photoreceptors. Five of 10 subjects had sensorineural hearing loss. The previously unreported missense variant (c.1115C g A, p.(Pro372His)) was found in 5 of 8 (62.5%) study families. Haplotype reconstruction using WGS data demonstrated a likely ancestral haplotype.ConclusionsFDXR-associated disease is a phenotypically heterogeneous disorder with retinal dystrophy being a major clinical feature observed in this cohort. In addition, we hypothesize that a number of factors are likely to drive the pathogenesis of optic atrophy, retinal degeneration, and perhaps the associated systemic manifestations. |
| Databáze: | OpenAIRE |
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