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Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature
PURPOSE: The 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. METHODS: Patients carrying biallelic candidate FDXR variants were identified by whole genome sequencing (WGS) as par...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107637/ https://www.ncbi.nlm.nih.gov/pubmed/33938912 http://dx.doi.org/10.1167/iovs.62.6.2 |
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author | 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 |
author_facet | 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 |
author_sort | Jurkute, Neringa |
collection | PubMed |
description | PURPOSE: The 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. METHODS: Patients 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. RESULTS: Ten 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. CONCLUSIONS: FDXR-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. |
format | Online Article Text |
id | pubmed-8107637 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
spelling | pubmed-81076372021-05-17 Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature 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 Invest Ophthalmol Vis Sci Genetics PURPOSE: The 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. METHODS: Patients 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. RESULTS: Ten 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. CONCLUSIONS: FDXR-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. The Association for Research in Vision and Ophthalmology 2021-05-03 /pmc/articles/PMC8107637/ /pubmed/33938912 http://dx.doi.org/10.1167/iovs.62.6.2 Text en Copyright 2021 The Authors https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License. |
spellingShingle | Genetics 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 Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature |
title | Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature |
title_full | Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature |
title_fullStr | Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature |
title_full_unstemmed | Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature |
title_short | Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature |
title_sort | expanding the fdxr-associated disease phenotype: retinal dystrophy is a recurrent ocular feature |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107637/ https://www.ncbi.nlm.nih.gov/pubmed/33938912 http://dx.doi.org/10.1167/iovs.62.6.2 |
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