PDF(Pubmed)
Abstract：
Advances in gene therapy and genome editing give hope that new treatments will soon be available for inherited eye diseases that together affect a significant proportion of the adult population. New solutions are needed to make genetic diagnosis fast and affordable. This is the first study of such a large group of patients with inherited retinal dystrophies (IRD) and inherited optic neuropathies (ION) in the Polish population. It is based on four years of diagnostic analysis using a broad, targeted NGS approach. The results include the most common pathogenic variants, as well as 91 novel causative variants, including frameshifts in the cumbersome RPGR ORF15 region. The high frequency of the ABCA4 complex haplotype p.(Leu541Pro;Ala1038Val) was confirmed. Additionally, a deletion of exons 22-24 in USH2A, probably specific to the Polish population, was uncovered as the most frequent copy number variation. The diagnostic yield of the broad NGS panel reached 64.3% and is comparable to the results reported for genetic studies of IRD and ION performed for other populations with more extensive WES or WGS methods. A combined approach to identify genetic causes of all known diseases manifesting in the posterior eye segment appears to be the optimal choice given the currently available treatment options and advanced clinical trials.
摘要：
基因治疗和基因组编辑的进展给人们带来了希望，新的治疗方法将很快用于遗传性眼病，这些疾病共同影响了相当大比例的成年人。需要新的解决方案来快速和负担得起基因诊断。这是波兰人群中如此庞大的遗传性视网膜营养不良（IRD）和遗传性视神经病变（ION）患者的首次研究。它基于四年的诊断分析，使用广泛的，有针对性的NGS方法。结果包括最常见的致病变异，以及91种新颖的致病变体，包括繁琐的RPGRORF15地区的移码。证实了ABCA4复合物单倍型p.(Leu541Pro;Ala1038Val)的高频率。此外,USH2A中外显子22-24的缺失，可能特定于波兰人口，被发现是最常见的拷贝数变异。广泛的NGS面板的诊断率达到64.3％，与使用更广泛的WES或WGS方法对其他人群进行的IRD和ION的遗传研究报告的结果相当。鉴于目前可用的治疗选择和先进的临床试验，一种联合方法来识别在后眼节表现的所有已知疾病的遗传原因似乎是最佳选择。
