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Genetic and clinical landscape of ARR3-associated MYP26: the most common cause of Mendelian early-onset high myopia with a unique inheritance

AIMS: To elucidate genetic background of early-onset high myopia (eoHM) and characteristics of ARR3-associated MYP26. METHODS: Variants in 14 genes reported to contribute to eoHM, including ARR3, were selected from exome sequencing data set and classified into different categories following American...

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Autores principales: Wang, Yingwei, Xiao, Xueshan, Li, Xueqing, Yi, Zhen, Jiang, Yi, Zhang, Fengsheng, Zhou, Lin, Li, Shiqiang, Jia, Xiaoyun, Sun, Wenmin, Wang, Panfeng, Zhang, Qingjiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10579186/
https://www.ncbi.nlm.nih.gov/pubmed/36180177
http://dx.doi.org/10.1136/bjo-2022-321511
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author Wang, Yingwei
Xiao, Xueshan
Li, Xueqing
Yi, Zhen
Jiang, Yi
Zhang, Fengsheng
Zhou, Lin
Li, Shiqiang
Jia, Xiaoyun
Sun, Wenmin
Wang, Panfeng
Zhang, Qingjiong
author_facet Wang, Yingwei
Xiao, Xueshan
Li, Xueqing
Yi, Zhen
Jiang, Yi
Zhang, Fengsheng
Zhou, Lin
Li, Shiqiang
Jia, Xiaoyun
Sun, Wenmin
Wang, Panfeng
Zhang, Qingjiong
author_sort Wang, Yingwei
collection PubMed
description AIMS: To elucidate genetic background of early-onset high myopia (eoHM) and characteristics of ARR3-associated MYP26. METHODS: Variants in 14 genes reported to contribute to eoHM, including ARR3, were selected from exome sequencing data set and classified into different categories following American College of Medical Genetics and Genomics guidelines based on in silico prediction, associated phenotypes, confirmation and cosegregation analysis. The available clinical data of individuals were summarised. RESULTS: Pathogenic and likely pathogenic variants in three of 14 genes were identified in 52 of 928 families with eoHM, including 29 in ARR3, 22 in OPN1LW and 1 in LRPAP1. For ARR3, 24 pathogenic variants (16 truncation and 8 missense) were identified in 66 women and 12 men, in whom 64 women and 4 men had eoHM by X-linked female-limited inheritance. Refraction ranged from −5.00 to −28.75 diopter (−12.58±4.83). Mild-to-moderately reduced cone responses were recorded in 76.9% (10/13) of patients with electroretinogram recordings. Most patients (75.9%, 41/54) had mild myopic fundus changes (C0 to C1). Genotype–phenotype analysis suggested that the myopic retinopathy degree was correlated with age and the variant’s nature. Peripheral retinal degeneration was observed in 38.5% (5/13) patients using wide-field examinations. CONCLUSION: This study reveals ARR3 as the most frequently implicated gene for Mendelian eoHM. Truncations and highly scored missense variants in ARR3 are pathogenic. Myopia due to ARR3 mutations is transmitted in X-linked female-limited inheritance, manifests with mild cone impairment and slowly progresses to pathologic myopia. Identification of the most common cause for Mendelian eoHM provides a valuable starting point into the molecular mechanism of myopia.
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spelling pubmed-105791862023-10-18 Genetic and clinical landscape of ARR3-associated MYP26: the most common cause of Mendelian early-onset high myopia with a unique inheritance Wang, Yingwei Xiao, Xueshan Li, Xueqing Yi, Zhen Jiang, Yi Zhang, Fengsheng Zhou, Lin Li, Shiqiang Jia, Xiaoyun Sun, Wenmin Wang, Panfeng Zhang, Qingjiong Br J Ophthalmol Clinical Science AIMS: To elucidate genetic background of early-onset high myopia (eoHM) and characteristics of ARR3-associated MYP26. METHODS: Variants in 14 genes reported to contribute to eoHM, including ARR3, were selected from exome sequencing data set and classified into different categories following American College of Medical Genetics and Genomics guidelines based on in silico prediction, associated phenotypes, confirmation and cosegregation analysis. The available clinical data of individuals were summarised. RESULTS: Pathogenic and likely pathogenic variants in three of 14 genes were identified in 52 of 928 families with eoHM, including 29 in ARR3, 22 in OPN1LW and 1 in LRPAP1. For ARR3, 24 pathogenic variants (16 truncation and 8 missense) were identified in 66 women and 12 men, in whom 64 women and 4 men had eoHM by X-linked female-limited inheritance. Refraction ranged from −5.00 to −28.75 diopter (−12.58±4.83). Mild-to-moderately reduced cone responses were recorded in 76.9% (10/13) of patients with electroretinogram recordings. Most patients (75.9%, 41/54) had mild myopic fundus changes (C0 to C1). Genotype–phenotype analysis suggested that the myopic retinopathy degree was correlated with age and the variant’s nature. Peripheral retinal degeneration was observed in 38.5% (5/13) patients using wide-field examinations. CONCLUSION: This study reveals ARR3 as the most frequently implicated gene for Mendelian eoHM. Truncations and highly scored missense variants in ARR3 are pathogenic. Myopia due to ARR3 mutations is transmitted in X-linked female-limited inheritance, manifests with mild cone impairment and slowly progresses to pathologic myopia. Identification of the most common cause for Mendelian eoHM provides a valuable starting point into the molecular mechanism of myopia. BMJ Publishing Group 2023-10 2022-09-30 /pmc/articles/PMC10579186/ /pubmed/36180177 http://dx.doi.org/10.1136/bjo-2022-321511 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
spellingShingle Clinical Science
Wang, Yingwei
Xiao, Xueshan
Li, Xueqing
Yi, Zhen
Jiang, Yi
Zhang, Fengsheng
Zhou, Lin
Li, Shiqiang
Jia, Xiaoyun
Sun, Wenmin
Wang, Panfeng
Zhang, Qingjiong
Genetic and clinical landscape of ARR3-associated MYP26: the most common cause of Mendelian early-onset high myopia with a unique inheritance
title Genetic and clinical landscape of ARR3-associated MYP26: the most common cause of Mendelian early-onset high myopia with a unique inheritance
title_full Genetic and clinical landscape of ARR3-associated MYP26: the most common cause of Mendelian early-onset high myopia with a unique inheritance
title_fullStr Genetic and clinical landscape of ARR3-associated MYP26: the most common cause of Mendelian early-onset high myopia with a unique inheritance
title_full_unstemmed Genetic and clinical landscape of ARR3-associated MYP26: the most common cause of Mendelian early-onset high myopia with a unique inheritance
title_short Genetic and clinical landscape of ARR3-associated MYP26: the most common cause of Mendelian early-onset high myopia with a unique inheritance
title_sort genetic and clinical landscape of arr3-associated myp26: the most common cause of mendelian early-onset high myopia with a unique inheritance
topic Clinical Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10579186/
https://www.ncbi.nlm.nih.gov/pubmed/36180177
http://dx.doi.org/10.1136/bjo-2022-321511
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