Adult-onset primary open-angle glaucoma caused by mutations in optineurin
Adult-onset primary open-angle glaucoma caused by mutations in optineurin
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DOI：
10.1126/science.1066901
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发表时间：
2002-02-08
期刊：
影响因子：
56.9
通讯作者：
Sarfarazi, M
中科院分区：
文献类型：
--
作者：
Rezaie, T;Child, A;Sarfarazi, M
原发性开角型青光眼（POAG）影响全球3300万人，是致盲的主要原因。在一项对54个常染色体显性遗传成人型POAG家族的研究中，我们在染色体10p14上发现了致病基因，并将其命名为OPTN （optinurin）。在16.7%的遗传性POAG家族中发现OPTN序列改变，包括眼压正常的个体。OPTN基因编码一个保守的66千道尔顿蛋白，其功能未知，与肿瘤坏死因子- α信号通路有关，并与多种蛋白相互作用，包括亨廷顿蛋白、ras相关蛋白RABB和转录因子IIIA。optinurin在小梁网、非色素纤毛上皮、视网膜和脑中表达，我们推测它具有神经保护作用。
Primary open-angle glaucoma (POAG) affects 33 million individuals worldwide and is a leading cause of blindness. In a study of 54 families with autosomal dominantly inherited adult-onset POAG, we identified the causative gene on chromosome 10p14 and designated it OPTN (for "optineurin"). Sequence alterations in OPTN were found in 16.7% of families with hereditary POAG, including individuals with normal intraocular pressure. The OPTN gene codes for a conserved 66-kilodalton protein of unknown function that has been implicated in the tumor necrosis factor-alpha signaling pathway and that interacts with diverse proteins including Huntingtin, Ras-associated protein RABB, and transcription factor IIIA. Optineurin is expressed in trabecular meshwork, nonpigmented ciliary epithelium, retina, and brain, and we speculate that it plays a neuroprotective role.