School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, 325027, China.
College of Engineering, Boston University, Boston, MA, USA.
Gene Ther. 2023 Feb;30(1-2):160-166. doi: 10.1038/s41434-022-00352-3. Epub 2022 Jul 6.
X-linked retinitis pigmentosa (XLRP) is the most severe form of Retinitis Pigmentosa (RP) and one of the leading causes of blindness in the world. Currently, there is no effective treatment for RP. In the present study, we recruited a XLRP family and identified a 4 bp deletion mutation (c. 2234_2237del) in RPGR ORF15 with Sanger sequencing, which was located in the exact same region as the missing XES (X chromosome exome sequencing) coverage. Then, we generated cell lines harboring the identified mutation and corrected it via enhanced prime editing system (ePE). Collectively, Sanger sequencing identified a pathogenic mutation in RPGR ORF15 for XLRP which was corrected with ePE. This study provides a valuable insight for genetic counseling of the afflicted family members and prenatal diagnosis, also paves a way for applying prime editing based gene therapy in those patients.
X 连锁性视网膜炎（XLRP）是视网膜炎（RP）中最严重的形式，也是世界上导致失明的主要原因之一。目前，RP 还没有有效的治疗方法。在本研究中，我们招募了一个 XLRP 家族，并通过 Sanger 测序发现了一个 RPGR ORF15 中的 4bp 缺失突变（c.2234_2237del），该突变位于与缺失的 XES（X 染色体外显子组测序）覆盖范围完全相同的区域。然后，我们构建了携带该鉴定突变的细胞系，并通过增强型 Prime Editing 系统（ePE）进行了校正。综上所述，通过 Sanger 测序鉴定了 RPGR ORF15 中的一个致病性突变，并通过 ePE 进行了校正。该研究为受累家庭成员的遗传咨询和产前诊断提供了有价值的见解，也为在这些患者中应用基于 Prime Editing 的基因治疗铺平了道路。
