{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:33:22Z","timestamp":1792805602533,"version":"4.5.0"},"reference-count":35,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770965"],"award-info":[{"award-number":["81770965"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Br J Ophthalmol"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To elucidate genetic background of early-onset high myopia (eoHM) and characteristics of<jats:italic>ARR3<\/jats:italic>-associated MYP26.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Variants in 14 genes reported to contribute to eoHM, including<jats:italic>ARR3<\/jats:italic>, 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pathogenic and likely pathogenic variants in three of 14 genes were identified in 52 of 928 families with eoHM, including 29 in<jats:italic>ARR3<\/jats:italic>, 22 in<jats:italic>OPN1LW<\/jats:italic>and 1 in<jats:italic>LRPAP1<\/jats:italic>. For<jats:italic>ARR3<\/jats:italic>, 24 pathogenic variants (16 truncation and 8 missense) were identified in 66\u2009women and 12 men, in whom 64\u2009women and 4 men had eoHM by X-linked female-limited inheritance. Refraction ranged from \u22125.00 to \u221228.75 diopter (\u221212.58\u00b14.83). 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\u2013phenotype analysis suggested that the myopic retinopathy degree was correlated with age and the variant\u2019s nature. Peripheral retinal degeneration was observed in 38.5% (5\/13) patients using wide-field examinations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study reveals<jats:italic>ARR3<\/jats:italic>as the most frequently implicated gene for Mendelian eoHM. Truncations and highly scored missense variants in<jats:italic>ARR3<\/jats:italic>are pathogenic. Myopia due to<jats:italic>ARR3<\/jats:italic>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.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bjo-2022-321511","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T17:25:16Z","timestamp":1664558716000},"page":"1545-1553","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Genetic and clinical landscape of<i>ARR3<\/i>-associated MYP26: the most common cause of Mendelian early-onset high myopia with a unique inheritance"],"prefix":"10.1136","volume":"107","author":[{"given":"Yingwei","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueshan","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6288-9154","authenticated-orcid":false,"given":"Xueqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengsheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenmin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panfeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7508-848X","authenticated-orcid":false,"given":"Qingjiong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"2023092102150608000_107.10.1545.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2016.01.006"},{"key":"2023092102150608000_107.10.1545.2","doi-asserted-by":"crossref","first-page":"e144","DOI":"10.1016\/S2214-109X(20)30489-7","article-title":"Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to vision 2020: the right to sight: an analysis for the global burden of disease study","volume":"9","year":"2021","journal-title":"Lancet Glob Health"},{"key":"2023092102150608000_107.10.1545.3","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac004"},{"key":"2023092102150608000_107.10.1545.4","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1001\/jamaophthalmol.2019.4421","article-title":"Association between polygenic risk score and risk of myopia","volume":"138","author":"Ghorbani Mojarrad","year":"2020","journal-title":"JAMA Ophthalmol"},{"key":"2023092102150608000_107.10.1545.5","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1001\/jamaophthalmol.2021.0497","article-title":"Evaluation of shared genetic susceptibility to high and low myopia and hyperopia","volume":"139","author":"Tideman","year":"2021","journal-title":"JAMA Ophthalmol"},{"key":"2023092102150608000_107.10.1545.6","doi-asserted-by":"crossref","unstructured":"Zhang Q . 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