Cargando…
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...
Autores principales: | , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1785076538134233088 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10362925 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT stephensonkirkaj ushersyndromeontheislandofirelandagenotypephenotypereview AT whelanlaura ushersyndromeontheislandofirelandagenotypephenotypereview AT zhujulia ushersyndromeontheislandofirelandagenotypephenotypereview AT dockeryadrian ushersyndromeontheislandofirelandagenotypephenotypereview AT wynneniamhc ushersyndromeontheislandofirelandagenotypephenotypereview AT cairnsrebeccam ushersyndromeontheislandofirelandagenotypephenotypereview AT kirkclaire ushersyndromeontheislandofirelandagenotypephenotypereview AT turnerjacqueline ushersyndromeontheislandofirelandagenotypephenotypereview AT duignanemmas ushersyndromeontheislandofirelandagenotypephenotypereview AT obyrnejamesj ushersyndromeontheislandofirelandagenotypephenotypereview AT silvestrigiuliana ushersyndromeontheislandofirelandagenotypephenotypereview AT kennapaulf ushersyndromeontheislandofirelandagenotypephenotypereview AT farrargjane ushersyndromeontheislandofirelandagenotypephenotypereview AT keegandavidj ushersyndromeontheislandofirelandagenotypephenotypereview |