State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong, China.
Department of Ophthalmology, Chaoju Inner Mongolia Eye Hospital Co Ltd, Hohhot, China.
Br J Ophthalmol. 2023 Oct;107(10):1545-1553. doi: 10.1136/bjo-2022-321511. Epub 2022 Sep 30.
To elucidate genetic background of early-onset high myopia (eoHM) and characteristics of -associated MYP26.
Variants in 14 genes reported to contribute to eoHM, including , 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.
Pathogenic and likely pathogenic variants in three of 14 genes were identified in 52 of 928 families with eoHM, including 29 in , 22 in and 1 in . For , 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.
This study reveals as the most frequently implicated gene for Mendelian eoHM. Truncations and highly scored missense variants in are pathogenic. Myopia due to 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.
阐明早发性高度近视（eoHM）的遗传背景和 -associated MYP26 的特征。
从外显子组测序数据集中选择了 14 个已知与 eoHM 相关的基因中的变异，根据美国医学遗传学与基因组学学院的指南，根据计算机预测、相关表型、确认和共分离分析，将这些变异分为不同类别。总结了个体的可用临床数据。
在 928 个 eoHM 家系中，有 52 个家系的 14 个基因中发现了致病性和可能致病性变异，包括 29 个在 中，22 个在 中，1 个在 中。对于 ，在 66 名女性和 12 名男性中发现了 24 个致病性变异（16 个截断和 8 个错义），其中 64 名女性和 4 名男性通过 X 连锁女性限性遗传患有 eoHM。屈光度范围为-5.00 至-28.75 屈光度（-12.58±4.83）。在进行视网膜电图记录的 13 名患者中，有 76.9%（10/13）记录到轻度至中度减弱的锥体反应。大多数患者（75.9%，41/54）有轻度近视眼底改变（C0 至 C1）。基因型-表型分析表明，近视性视网膜病变的严重程度与年龄和变异的性质有关。使用广角检查发现 38.5%（5/13）的患者有周边视网膜变性。
本研究揭示 是常染色体显性 eoHM 最常涉及的基因。 中的截断和高分错义变异是致病性的。由 突变引起的近视以 X 连锁女性限性遗传方式传递，表现为轻度锥体损伤，并缓慢进展为病理性近视。确定常染色体显性 eoHM 的最常见原因提供了一个有价值的起点，了解近视的分子机制。
