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Usher Syndrome on the Island of Ireland: A Genotype-Phenotype Review

PURPOSE: Usher syndrome (USH) is a genetically heterogeneous group of autosomal recessive (AR) syndromic inherited retinal degenerations (IRDs) representing 50% of deaf-blindness. All subtypes include retinitis pigmentosa, sensorineural hearing loss, and vestibular abnormalities. Thorough phenotypin...

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Autores principales: Stephenson, Kirk A. J., Whelan, Laura, Zhu, Julia, Dockery, Adrian, Wynne, Niamh C., Cairns, Rebecca M., Kirk, Claire, Turner, Jacqueline, Duignan, Emma S., O'Byrne, James J., Silvestri, Giuliana, Kenna, Paul F., Farrar, G. Jane, Keegan, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362925/
https://www.ncbi.nlm.nih.gov/pubmed/37466950
http://dx.doi.org/10.1167/iovs.64.10.23
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author Stephenson, Kirk A. J.
Whelan, Laura
Zhu, Julia
Dockery, Adrian
Wynne, Niamh C.
Cairns, Rebecca M.
Kirk, Claire
Turner, Jacqueline
Duignan, Emma S.
O'Byrne, James J.
Silvestri, Giuliana
Kenna, Paul F.
Farrar, G. Jane
Keegan, David J.
author_facet Stephenson, Kirk A. J.
Whelan, Laura
Zhu, Julia
Dockery, Adrian
Wynne, Niamh C.
Cairns, Rebecca M.
Kirk, Claire
Turner, Jacqueline
Duignan, Emma S.
O'Byrne, James J.
Silvestri, Giuliana
Kenna, Paul F.
Farrar, G. Jane
Keegan, David J.
author_sort Stephenson, Kirk A. J.
collection PubMed
description PURPOSE: Usher syndrome (USH) is a genetically heterogeneous group of autosomal recessive (AR) syndromic inherited retinal degenerations (IRDs) representing 50% of deaf-blindness. All subtypes include retinitis pigmentosa, sensorineural hearing loss, and vestibular abnormalities. Thorough phenotyping may facilitate genetic diagnosis and intervention. Here we report the clinical/genetic features of an Irish USH cohort. METHODS: USH patients were selected from the Irish IRD registry (Target 5000). Patients were examined clinically (deep-phenotyping) and genetically using a 254 IRD–associated gene target capture sequencing panel, USH2A exon, and whole genome sequencing. RESULTS: The study identified 145 patients (24.1% USH1 [n = 35], 73.8% USH2 [n = 107], 1.4% USH3 [n = 2], and 0.7% USH4 [n = 1]). A genetic diagnosis was reached in 82.1%, the majority (80.7%) being MYO7A or USH2A genotypes. Mean visual acuity and visual field (VF) were 0.47 ± 0.58 LogMAR and 31.3° ± 32.8°, respectively, at a mean age of 43 years. Legal blindness criteria were met in 40.7%. Cataract was present in 77.4%. ADGRV1 genotypes had the most VF loss, whereas USH2A patients had greater myopia and CDH23 had the most astigmatism. Variants absent from gnomAD non-Finnish Europeans and ClinVar represented more than 20% of the variants identified and were detected in ADGRV1, ARSG, CDH23, MYO7A, and USH2A. CONCLUSIONS: USH is a genetically diverse group of AR IRDs that have a profound impact on affected individuals and their families. The prevalence and phenotype/genotype characteristics of USH in Ireland have, as yet, gone unreported. Understanding the genotype of Irish USH patients may guide clinical and genetic characterization facilitating access to existing/novel therapeutics.
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spelling pubmed-103629252023-07-23 Usher Syndrome on the Island of Ireland: A Genotype-Phenotype Review Stephenson, Kirk A. J. Whelan, Laura Zhu, Julia Dockery, Adrian Wynne, Niamh C. Cairns, Rebecca M. Kirk, Claire Turner, Jacqueline Duignan, Emma S. O'Byrne, James J. Silvestri, Giuliana Kenna, Paul F. Farrar, G. Jane Keegan, David J. Invest Ophthalmol Vis Sci Genetics PURPOSE: Usher syndrome (USH) is a genetically heterogeneous group of autosomal recessive (AR) syndromic inherited retinal degenerations (IRDs) representing 50% of deaf-blindness. All subtypes include retinitis pigmentosa, sensorineural hearing loss, and vestibular abnormalities. Thorough phenotyping may facilitate genetic diagnosis and intervention. Here we report the clinical/genetic features of an Irish USH cohort. METHODS: USH patients were selected from the Irish IRD registry (Target 5000). Patients were examined clinically (deep-phenotyping) and genetically using a 254 IRD–associated gene target capture sequencing panel, USH2A exon, and whole genome sequencing. RESULTS: The study identified 145 patients (24.1% USH1 [n = 35], 73.8% USH2 [n = 107], 1.4% USH3 [n = 2], and 0.7% USH4 [n = 1]). A genetic diagnosis was reached in 82.1%, the majority (80.7%) being MYO7A or USH2A genotypes. Mean visual acuity and visual field (VF) were 0.47 ± 0.58 LogMAR and 31.3° ± 32.8°, respectively, at a mean age of 43 years. Legal blindness criteria were met in 40.7%. Cataract was present in 77.4%. ADGRV1 genotypes had the most VF loss, whereas USH2A patients had greater myopia and CDH23 had the most astigmatism. Variants absent from gnomAD non-Finnish Europeans and ClinVar represented more than 20% of the variants identified and were detected in ADGRV1, ARSG, CDH23, MYO7A, and USH2A. CONCLUSIONS: USH is a genetically diverse group of AR IRDs that have a profound impact on affected individuals and their families. The prevalence and phenotype/genotype characteristics of USH in Ireland have, as yet, gone unreported. Understanding the genotype of Irish USH patients may guide clinical and genetic characterization facilitating access to existing/novel therapeutics. The Association for Research in Vision and Ophthalmology 2023-07-19 /pmc/articles/PMC10362925/ /pubmed/37466950 http://dx.doi.org/10.1167/iovs.64.10.23 Text en Copyright 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Genetics
Stephenson, Kirk A. J.
Whelan, Laura
Zhu, Julia
Dockery, Adrian
Wynne, Niamh C.
Cairns, Rebecca M.
Kirk, Claire
Turner, Jacqueline
Duignan, Emma S.
O'Byrne, James J.
Silvestri, Giuliana
Kenna, Paul F.
Farrar, G. Jane
Keegan, David J.
Usher Syndrome on the Island of Ireland: A Genotype-Phenotype Review
title Usher Syndrome on the Island of Ireland: A Genotype-Phenotype Review
title_full Usher Syndrome on the Island of Ireland: A Genotype-Phenotype Review
title_fullStr Usher Syndrome on the Island of Ireland: A Genotype-Phenotype Review
title_full_unstemmed Usher Syndrome on the Island of Ireland: A Genotype-Phenotype Review
title_short Usher Syndrome on the Island of Ireland: A Genotype-Phenotype Review
title_sort usher syndrome on the island of ireland: a genotype-phenotype review
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362925/
https://www.ncbi.nlm.nih.gov/pubmed/37466950
http://dx.doi.org/10.1167/iovs.64.10.23
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