Genomic Landscape and Natural History of Sector Retinitis Pigmentosa
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://doi.org/10.48560/rspo.25958 |
Resumo: | Introduction: Sector retinitis pigmentosa (sRP) is a rare, atypical, and milder variant of rod-cone degeneration. Despite historically associated with RHO gene, the mutational spectrum of sRP is evolving with multiple causative genes recently implicated. This study aimed to characterize the genotypes, phenotypes, and natural history of a Portuguese cohort of sRP. Methods: Retrospective, observational study, conducted at a tertiary referral center. Patients with a clinical diagnosis of sRP and available genetic testing results were identified using a web-based registry. The clinical diagnosis was established based on ophthalmologic examination, functional testing [best corrected visual acuity (BCVA) and visual field testing] and multimodal imaging [color fundus photography (CFP), fundus autofluorescence (FAF) and optical coherence tomography (OCT)]. Genetic testing was clinically oriented in all probands, and variants were classified according to the American College of Medical Genetics and Genomics. Only likely pathogenic or pathogenic variants were considered disease-causing. Clinical progression was evaluated throughout follow-up. Results: Fourteen patients from twelve families were included. Disease-causing variants in RP-related genes were identified in 8 families, for a diagnostic yield of 66.7%. EYS was the most frequently implicated gene (4 families), followed by RHO (2 families), and finally MYO7A and NPHP1 (1 family each). In most unsolved cases, no clinically significant variants were found. However, for one unsolved case, a RHO-associated variant of uncertain significance was identified. Two patients exhibited syndromic sRP. All cases were bilateral and symmetrical except for two. Inferior and/or nasal retinal involvement on FAF was noted in all cases. Visual field testing revealed superior field defects of varying extents, always in close association with observed FAF findings. Over a median follow-up of 32.5 months (range: 5-148 months), no significant differences were found on BCVA (p=0.056). In fact, BCVA remained stable and ≤ 0.20 LogMAR OU in 9/14 patients. Multimodal imaging revealed no progression over the available follow-up. Conclusion: This study highlights the genotypic heterogeneity of sRP in a Portuguese cohort. Inferior and nasal predilection was common across different genotypes, and a high proportion of patients maintained good central vision. The longitudinal data provided herein will help to accurately inform patients on prognosis. |
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Genomic Landscape and Natural History of Sector Retinitis PigmentosaVariabilidade Genómica e História Natural da Retinopatia Pigmentar SectorialArtigos OriginaisIntroduction: Sector retinitis pigmentosa (sRP) is a rare, atypical, and milder variant of rod-cone degeneration. Despite historically associated with RHO gene, the mutational spectrum of sRP is evolving with multiple causative genes recently implicated. This study aimed to characterize the genotypes, phenotypes, and natural history of a Portuguese cohort of sRP. Methods: Retrospective, observational study, conducted at a tertiary referral center. Patients with a clinical diagnosis of sRP and available genetic testing results were identified using a web-based registry. The clinical diagnosis was established based on ophthalmologic examination, functional testing [best corrected visual acuity (BCVA) and visual field testing] and multimodal imaging [color fundus photography (CFP), fundus autofluorescence (FAF) and optical coherence tomography (OCT)]. Genetic testing was clinically oriented in all probands, and variants were classified according to the American College of Medical Genetics and Genomics. Only likely pathogenic or pathogenic variants were considered disease-causing. Clinical progression was evaluated throughout follow-up. Results: Fourteen patients from twelve families were included. Disease-causing variants in RP-related genes were identified in 8 families, for a diagnostic yield of 66.7%. EYS was the most frequently implicated gene (4 families), followed by RHO (2 families), and finally MYO7A and NPHP1 (1 family each). In most unsolved cases, no clinically significant variants were found. However, for one unsolved case, a RHO-associated variant of uncertain significance was identified. Two patients exhibited syndromic sRP. All cases were bilateral and symmetrical except for two. Inferior and/or nasal retinal involvement on FAF was noted in all cases. Visual field testing revealed superior field defects of varying extents, always in close association with observed FAF findings. Over a median follow-up of 32.5 months (range: 5-148 months), no significant differences were found on BCVA (p=0.056). In fact, BCVA remained stable and ≤ 0.20 LogMAR OU in 9/14 patients. Multimodal imaging revealed no progression over the available follow-up. Conclusion: This study highlights the genotypic heterogeneity of sRP in a Portuguese cohort. Inferior and nasal predilection was common across different genotypes, and a high proportion of patients maintained good central vision. The longitudinal data provided herein will help to accurately inform patients on prognosis.Introdução: A retinopatia pigmentar setorial (sRP) é uma forma rara, atípica e menos severa de distrofia de bastonetes-cones. Apesar de tipicamente associada ao gene RHO, o espetro mutacional da sRP está em evolução, com múltiplos novos genes recentemente associados. O objectivo deste estudo é caracterizar os genótipos, fenótipos e história natural da sRP numa coorte portuguesa. Métodos: Estudo retrospetivo, observacional. Identificámos doentes com diagnostico clínico de sRP e com resultados genéticos disponíveis. O diagnóstico clínico foi baseado no exame oftalmológico, avaliação funcional (acuidade visual corrigida e avaliação de campos visuais) e imagiologia retiniana multimodal (retinografia, autofluorescência do fundo ocular e tomografia de coerência ótica). O estudo genético foi direcionado com base na informação clínica e as variantes genéticas encontradas foram classificadas de acordo com orientações do American College of Medical Genetics and Genomics. Variantes patogénicas ou provavelmente patogénicas foram consideradas causadoras de doença. A progressão clínica foi avaliada ao longo do follow-up. Resultados: Foram incluídos 14 doentes (12 famílias). Foram identificadas variantes genéticas causadoras de doença em 8 famílias, resultando numa taxa de diagnostico de 66.7%. EYS foi o gene mais frequentemente encontrado (4 famílias), seguido de RHO (2 famílias) e finalmente MYO7A e NPHP1 (1 família cada). Num dos casos sem confirmação genética foi identificada uma variante de significado incerto no gene RHO. Dois pacientes exibiam sRP sindrómica. Todos os casos eram bilaterais e simétricos exceto dois. Na autofluorescência foi detetado envolvimento da retina nasal e/ou inferior em todos os doentes. Não se verificaram diferenças estatisticamente significativas (p=0.056) na melhor acuidade visual corrigida ao longo de um follow-up mediano de 32.5 meses (variação: 5-148 meses). A visão manteve-se estável e ≤ 0.20 LogMAR OU em 9/14 doentes. Não foi detetada progressão em imagem multimodal ao longo do follow-up disponível. Conclusão: Este estudo destaca a heterogeneidade genotípica da sRP numa coorte portuguesa. Envolvimento inferior e nasal foi comum a todos os casos e uma grande parte dos doentes manteve uma boa acuidade visual. Os dados apresentados serão uteis para aconselhar os pacientes em relação ao prognostico desta doença. Ajnet2022-04-10T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://doi.org/10.48560/rspo.25958eng1646-69501646-6950Cortinhal, TelmoGeada, SaraNeves, EmmanuelCarvalho, Ana LuísaSaraiva, JorgeSilva, RufinoMurta, JoaquimMarques, João Pedroinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-09-22T17:06:17Zoai:ojs.revistas.rcaap.pt:article/25958Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:01:47.721866Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Genomic Landscape and Natural History of Sector Retinitis Pigmentosa Variabilidade Genómica e História Natural da Retinopatia Pigmentar Sectorial |
title |
Genomic Landscape and Natural History of Sector Retinitis Pigmentosa |
spellingShingle |
Genomic Landscape and Natural History of Sector Retinitis Pigmentosa Cortinhal, Telmo Artigos Originais |
title_short |
Genomic Landscape and Natural History of Sector Retinitis Pigmentosa |
title_full |
Genomic Landscape and Natural History of Sector Retinitis Pigmentosa |
title_fullStr |
Genomic Landscape and Natural History of Sector Retinitis Pigmentosa |
title_full_unstemmed |
Genomic Landscape and Natural History of Sector Retinitis Pigmentosa |
title_sort |
Genomic Landscape and Natural History of Sector Retinitis Pigmentosa |
author |
Cortinhal, Telmo |
author_facet |
Cortinhal, Telmo Geada, Sara Neves, Emmanuel Carvalho, Ana Luísa Saraiva, Jorge Silva, Rufino Murta, Joaquim Marques, João Pedro |
author_role |
author |
author2 |
Geada, Sara Neves, Emmanuel Carvalho, Ana Luísa Saraiva, Jorge Silva, Rufino Murta, Joaquim Marques, João Pedro |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Cortinhal, Telmo Geada, Sara Neves, Emmanuel Carvalho, Ana Luísa Saraiva, Jorge Silva, Rufino Murta, Joaquim Marques, João Pedro |
dc.subject.por.fl_str_mv |
Artigos Originais |
topic |
Artigos Originais |
description |
Introduction: Sector retinitis pigmentosa (sRP) is a rare, atypical, and milder variant of rod-cone degeneration. Despite historically associated with RHO gene, the mutational spectrum of sRP is evolving with multiple causative genes recently implicated. This study aimed to characterize the genotypes, phenotypes, and natural history of a Portuguese cohort of sRP. Methods: Retrospective, observational study, conducted at a tertiary referral center. Patients with a clinical diagnosis of sRP and available genetic testing results were identified using a web-based registry. The clinical diagnosis was established based on ophthalmologic examination, functional testing [best corrected visual acuity (BCVA) and visual field testing] and multimodal imaging [color fundus photography (CFP), fundus autofluorescence (FAF) and optical coherence tomography (OCT)]. Genetic testing was clinically oriented in all probands, and variants were classified according to the American College of Medical Genetics and Genomics. Only likely pathogenic or pathogenic variants were considered disease-causing. Clinical progression was evaluated throughout follow-up. Results: Fourteen patients from twelve families were included. Disease-causing variants in RP-related genes were identified in 8 families, for a diagnostic yield of 66.7%. EYS was the most frequently implicated gene (4 families), followed by RHO (2 families), and finally MYO7A and NPHP1 (1 family each). In most unsolved cases, no clinically significant variants were found. However, for one unsolved case, a RHO-associated variant of uncertain significance was identified. Two patients exhibited syndromic sRP. All cases were bilateral and symmetrical except for two. Inferior and/or nasal retinal involvement on FAF was noted in all cases. Visual field testing revealed superior field defects of varying extents, always in close association with observed FAF findings. Over a median follow-up of 32.5 months (range: 5-148 months), no significant differences were found on BCVA (p=0.056). In fact, BCVA remained stable and ≤ 0.20 LogMAR OU in 9/14 patients. Multimodal imaging revealed no progression over the available follow-up. Conclusion: This study highlights the genotypic heterogeneity of sRP in a Portuguese cohort. Inferior and nasal predilection was common across different genotypes, and a high proportion of patients maintained good central vision. The longitudinal data provided herein will help to accurately inform patients on prognosis. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-04-10T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://doi.org/10.48560/rspo.25958 |
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https://doi.org/10.48560/rspo.25958 |
dc.language.iso.fl_str_mv |
eng |
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eng |
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1646-6950 1646-6950 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Ajnet |
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Ajnet |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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