一个四代同堂的中国高度近视家系中角蛋白 12 基因突变。
A novel variant in the keratin 12 gene in a four-generation Chinese family with high myopia.
机构信息
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, 200000, China.
Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China.
出版信息
Eye (Lond). 2024 Dec;38(17):3290-3295. doi: 10.1038/s41433-024-03279-8. Epub 2024 Aug 2.
BACKGROUND
High myopia is a major cause of visual impairment, and genetic factors play crucial roles in the pathogenesis. We performed this study to identify candidate genes for the development of high myopia in a four-generation Chinese family with myopia.
METHODS
All family members with myopia and 100 healthy participants were included in this study. Data were obtained on demographics, disease history, and ocular examination results. We performed whole exome sequencing of the genomic DNA and Sanger sequencing to verify the variants. Functional analyses of the variant were performed using software programmes.
RESULTS
Nine of thirteen family members were found to have high myopia, amongst which two members were also diagnosed keratoconus. A missense variant in the keratin 12 gene (KRT12, p.Val410Gly) was detected in all high myopia cases but not in other family members without high myopia or the controls. The variant was predicted to be benign by online software programmes. However, modelling of the three-dimensional structure of the protein clearly revealed conformational changes caused by the mutation.
CONCLUSIONS
A missense mutation in the KRT12 gene was identified in this Chinese family, which may be associated with the pathogenesis of high myopia.
背景
高度近视是视力损害的主要原因，遗传因素在发病机制中起着至关重要的作用。我们进行这项研究是为了在一个四代中国近视家族中鉴定出导致高度近视的候选基因。
方法
本研究纳入了所有近视的家族成员和 100 名健康参与者。收集了人口统计学、疾病史和眼部检查结果的数据。我们对基因组 DNA 进行了全外显子测序，并对变异进行了 Sanger 测序验证。使用软件程序对变体进行了功能分析。
结果
13 名家族成员中有 9 名被发现患有高度近视，其中 2 名还被诊断为圆锥角膜。在所有高度近视病例中均检测到角蛋白 12 基因（KRT12，p.Val410Gly）中的错义变异，但在没有高度近视的其他家族成员或对照组中未检测到该变异。在线软件程序预测该变异是良性的。然而，对蛋白质三维结构的建模清楚地揭示了突变引起的构象变化。
结论
在这个中国家族中发现了角蛋白 12 基因的错义突变，该突变可能与高度近视的发病机制有关。
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