CLINICAL PROGRESS IN INHERITED RETINAL DEGENERATIONS: GENE THERAPY CLINICAL TRIALS AND ADVANCES IN GENETIC SEQUENCING.
CLINICAL PROGRESS IN INHERITED RETINAL DEGENERATIONS: GENE THERAPY CLINICAL TRIALS AND ADVANCES IN GENETIC SEQUENCING.
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DOI：
10.1097/iae.0000000000001341
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发表时间：
2017-03
期刊：
影响因子：
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通讯作者：
Hafler BP
中科院分区：
文献类型：
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作者：
Hafler BP
遗传性视网膜营养不良是导致视力丧失的一个重要原因，其特征是光感受器和视网膜色素上皮(RPE)的丧失。大约250个基因的突变导致遗传性视网膜变性，具有高度的遗传异质性。下一代测序的新技术使所有视网膜疾病基因的综合分析成为可能，从而改变了遗传性视网膜营养不良的分子诊断方法。这篇综述分析了基因诊断检测的临床进展和对视网膜基因治疗的启示。应用PubMed和OMIM数据库对遗传性视网膜营养不良的相关文献进行检索。下一代基因测序可以同时分析导致遗传性视网膜营养不良的所有大约250个基因。报告的诊断率范围很高，从51%到57%不等。这些新的测序工具具有很高的准确性，灵敏度为97.9%，特异度为100%。视网膜基因治疗的临床试验正在进行中，涉及多种基因，包括RPE65、ABCA4、CHM、RS1、MYO7A、CNGA3、CNGB3、ND4和MERTK，分子诊断可能对患者有利。对所有视网膜营养不良基因进行全面的下一代基因测序正在改变视网膜专家对遗传性视网膜变性进行基因测试的方式。不仅获得了高的诊断率，而且还鉴定了具有新的临床表型的基因突变。在视网膜基因治疗临床试验的时代，识别特定的基因缺陷将越来越多地用于识别可能参加临床研究并受益于新疗法的患者。
Inherited retinal dystrophies are a significant cause of vision loss and are characterized by the loss of photoreceptors and the retinal pigment epithelium (RPE). Mutations in approximately 250 genes cause inherited retinal degenerations with a high degree of genetic heterogeneity. New techniques in next-generation sequencing are allowing the comprehensive analysis of all retinal disease genes thus changing the approach to the molecular diagnosis of inherited retinal dystrophies. This review serves to analyze clinical progress in genetic diagnostic testing and implications for retinal gene therapy. A literature search of PubMed and OMIM was conducted to relevant articles in inherited retinal dystrophies. Next-generation genetic sequencing allows the simultaneous analysis of all the approximately 250 genes that cause inherited retinal dystrophies. Reported diagnostic rates range are high and range from 51% to 57%. These new sequencing tools are highly accurate with sensitivities of 97.9% and specificities of 100%. Retinal gene therapy clinical trials are underway for multiple genes including RPE65, ABCA4, CHM, RS1, MYO7A, CNGA3, CNGB3, ND4, and MERTK for which a molecular diagnosis may be beneficial for patients. Comprehensive next-generation genetic sequencing of all retinal dystrophy genes is changing the paradigm for how retinal specialists perform genetic testing for inherited retinal degenerations. Not only are high diagnostic yields obtained, but mutations in genes with novel clinical phenotypes are also identified. In the era of retinal gene therapy clinical trials, identifying specific genetic defects will increasingly be of use to identify patients who may enroll in clinical studies and benefit from novel therapies.