Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy
Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy
复制标题
DOI：
10.1038/s41598-018-38007-2
复制
发表时间：
2019-02-04
影响因子：
4.6
通讯作者：
Gronskov, Karen
中科院分区：
文献类型：
--
作者：
Jespersgaard, Cathrine;Fang, Mingyan;Gronskov, Karen
遗传性视网膜疾病（IRD）是视力障碍的常见原因。IRD涵盖了一组遗传上高度异质性的疾病，其中超过150个基因与一种或多种IRD临床形式相关。分子遗传学诊断变得越来越重要，特别是由于正在开发的基因治疗策略的数量不断增加。下一代基因组测序（NGS）已被证明是IRD的一种有价值的诊断工具。我们目前的分子研究结果的677人，居住在丹麦，与IRD和报告806变种，其中187是新的。我们发现跨越一个或多个外显子的缺失和重复可以解释3%的病例，因此拷贝数变异（CNV）分析在IRD的分子遗传学诊断中是重要的。7%的个体在一个以上的基因中具有被归类为致病性或可能致病性的变异。可能的丹麦创始人变异EYS和RP 1的报告。大量变异被归类为意义未知的变异;这些变异的报告有望有助于阐明实际的临床后果，使分类在未来不那么麻烦。总之，本研究强调了进行IRD靶向测序（包括CNV分析）的相关性以及与临床诊断相互作用的重要性。
Inherited retinal diseases (IRDs) are a common cause of visual impairment. IRD covers a set of genetically highly heterogeneous disorders with more than 150 genes associated with one or more clinical forms of IRD. Molecular genetic diagnosis has become increasingly important especially due to expanding number of gene therapy strategies under development. Next generation sequencing (NGS) of gene panels has proven a valuable diagnostic tool in IRD. We present the molecular findings of 677 individuals, residing in Denmark, with IRD and report 806 variants of which 187 are novel. We found that deletions and duplications spanning one or more exons can explain 3% of the cases, and thus copy number variation (CNV) analysis is important in molecular genetic diagnostics of IRD. Seven percent of the individuals have variants classified as pathogenic or likely-pathogenic in more than one gene. Possible Danish founder variants in EYS and RP1 are reported. A significant number of variants were classified as variants with unknown significance; reporting of these will hopefully contribute to the elucidation of the actual clinical consequence making the classification less troublesome in the future. In conclusion, this study underlines the relevance of performing targeted sequencing of IRD including CNV analysis as well as the importance of interaction with clinical diagnoses.