Division of Neurosciences, Biodonostia Health Research Institute, San Sebastián, Spain.
RETICS OFTARED, National Institute of Health Carlos III, Ministry of Economy and Competitiveness, Madrid, Spain.
Sci Rep. 2018 Oct 18;8(1):15457. doi: 10.1038/s41598-018-33810-3.
Inherited retinal diseases (IRD) are a heterogeneous group of diseases that mainly affect the retina; more than 250 genes have been linked to the disease and more than 20 different clinical phenotypes have been described. This heterogeneity both at the clinical and genetic levels complicates the identification of causative mutations. Therefore, a detailed genetic characterization is important for genetic counselling and decisions regarding treatment. In this study, we developed a method consisting on pooled targeted next generation sequencing (NGS) that we applied to 316 eye disease related genes, followed by High Resolution Melting and copy number variation analysis. DNA from 115 unrelated test samples was pooled and samples with known mutations were used as positive controls to assess the sensitivity of our approach. Causal mutations for IRDs were found in 36 patients achieving a detection rate of 31.3%. Overall, 49 likely causative mutations were identified in characterized patients, 14 of which were first described in this study (28.6%). Our study shows that this new approach is a cost-effective tool for detection of causative mutations in patients with inherited retinopathies.
遗传性视网膜疾病（IRD）是一组主要影响视网膜的异质性疾病；已经有 250 多个基因与该疾病相关，并且已经描述了 20 多种不同的临床表型。这种在临床和遗传水平上的异质性使得致病突变的识别变得复杂。因此，详细的遗传特征分析对于遗传咨询和治疗决策很重要。在这项研究中，我们开发了一种方法，包括汇集靶向的下一代测序（NGS），然后进行高分辨率熔解和拷贝数变异分析。将 115 个无关的测试样本汇集在一起，并使用已知突变的样本作为阳性对照，以评估我们方法的敏感性。在 36 名患者中发现了 IRD 的致病突变，检出率为 31.3%。总体而言，在已确诊的患者中发现了 49 个可能的致病突变，其中 14 个是首次在本研究中描述的（28.6%）。我们的研究表明，这种新方法是一种经济有效的工具，可用于检测遗传性视网膜疾病患者的致病突变。
