Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature
| Autor: | 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 |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Adolescent Visual Acuity Eye Ophthalmology & Optometry Medical and Health Sciences Retina Whole Exome Sequencing syndromic optic neuropathy Young Adult ferredoxin reductase Rare Diseases Clinical Research Retinal Dystrophies Exome Sequencing Electroretinography Genetics Humans 2.1 Biological and endogenous factors Aetiology retinal dystrophy Child Preschool Eye Disease and Disorders of Vision Retrospective Studies Human Genome Neurosciences Biological Sciences Pedigree Ferredoxin-NADP Reductase Phenotype Genomics England Research Consortium FDXR iron accumulation Mutation Female Missense neurodegenerative disorder Biotechnology |
| Zdroj: | Investigative ophthalmology & visual science, vol 62, iss 6 |
| Popis: | 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 > 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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