PDF(Pubmed)
Abstract：
Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability. Previous studies have shown the cost-effectiveness of sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in a cohort of patients diagnosed with Stargardt disease and other maculopathies. Methods: Here, we introduce a smMIPs panel that targets the exons and splice sites of all currently known genes associated with RP and LCA, the entire RPE65 gene, known causative deep-intronic variants leading to pseudo-exons, and part of the RP17 region associated with autosomal dominant RP, by using a total of 16,812 smMIPs. The RP-LCA smMIPs panel was used to screen 1,192 probands from an international cohort of predominantly RP and LCA cases. Results and discussion: After genetic analysis, a diagnostic yield of 56% was obtained which is on par with results from WES analysis. The effectiveness and the reduced costs compared to WES renders the RP-LCA smMIPs panel a competitive approach to provide IRD patients with a genetic diagnosis, especially in countries with restricted access to genetic testing.
摘要：
简介：色素性视网膜炎（RP）和Leber先天性黑蒙（LCA）是两组遗传性视网膜疾病（IRD），其中视杆光感受器退化，然后是视网膜的视锥光感受器。IRD的遗传诊断具有挑战性，因为>280个基因与这些疾病有关。虽然整个外显子组测序（WES）通常被诊断机构使用，成本和所需的基础设施阻碍了其全球适用性。先前的研究表明，在被诊断患有Stargardt病和其他黄斑病变的患者队列中，使用单分子分子反转探针（smMIP）进行序列分析的成本效益。方法:这里,我们引入了一个smMIPs小组，该小组针对与RP和LCA相关的所有当前已知基因的外显子和剪接位点，整个RPE65基因,已知的导致伪外显子的致病性深内含子变异，和部分与常染色体显性RP相关的RP17区域，通过使用总共16812个SMMIP。RP-LCAsmMIPs小组用于从主要为RP和LCA病例的国际队列中筛选1,192名先证者。结果与讨论：经过基因分析，获得56%的诊断率,与WES分析的结果相当.与WES相比，有效性和降低的成本使RP-LCAsmMIPs小组成为为IRD患者提供遗传诊断的竞争性方法，特别是在基因检测受到限制的国家。
