GLRA2gene mutations cause high myopia in humans and mice
| العنوان: | GLRA2gene mutations cause high myopia in humans and mice |
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| المؤلفون: | Qi Tian, Ping Tong, Gong Chen, Meichun Deng, Tian'e Cai, Runyi Tian, Zimin Zhang, Kun Xia, Zhengmao Hu |
| المصدر: | Journal of Medical Genetics. 60:193-203 |
| بيانات النشر: | BMJ, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Genetics, Genetics (clinical) |
| الوصف: | BackgroundHigh myopia (HM) is a leading cause of blindness that has a strong genetic predisposition. However, its genetic and pathogenic mechanisms remain largely unknown. Thus, this study aims to determine the genetic profile of individuals from two large Chinese families with HM and 200 patients with familial/sporadic HM. We also explored the pathogenic mechanism of HM using HEK293 cells and a mouse model.MethodsThe participants underwent genome-wide linkage analysis and exome sequencing. Visual acuity, electroretinogram response, refractive error, optical parameters and retinal rod cell genesis were measured in knockout mice. Immunofluorescent staining, biotin-labelled membrane protein isolation and electrophysiological characterisation were conducted in cells transfected with overexpression plasmids.ResultsA novel HM locus on Xp22.2-p11.4 was identified. Variant c.539C>T (p.Pro180Leu) inGLRA2gene was co-segregated with HM in the two families. Another variant, c.458G>A (p.Arg153Gln), was identified in a sporadic sample. TheGlra2knockout mice showed myopia-related phenotypes, decreased electroretinogram responses and impaired retinal rod cell genesis. Variants c.458G>A and c.539C>T altered the localisation of GlyRα2 on the cell membrane and decreased agonist sensitivity.ConclusionGLRA2was identified as a novel HM-causing gene. Its variants would cause HM through altered visual experience by impairing photoperception and visual transmission. |
| تدمد: | 1468-6244 0022-2593 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::26eda9010c4202f8b5255087c760a453 https://doi.org/10.1136/jmedgenet-2022-108425 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........26eda9010c4202f8b5255087c760a453 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14686244 00222593 |
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