Department of Ophthalmology, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China 100045.
Ophthalmic Genet. 2022 Jun;43(3):371-377. doi: 10.1080/13816810.2022.2039721. Epub 2022 Mar 7.
To identify mutations in patients with retinitis pigmentosa (RP) from our cohort and summarize the genotypes and phenotypes of reported previously.
Probands with RP phenotypes were recruited from our genetic retinopathy screening work. DNA was extracted from the peripheral venous blood, and exome sequencing was performed. We further examined the clinical data and family history in detail in these patients. mutations associated with RP were searched and summarized from the previous reports, and the results were combined with the data presented in our study. The mutation spectrum of was systematically analyzed, and the phenotypes of truncated mutations and missense mutations were compared and described.
Mutations in were detected in three families, including two novel mutations (c.2017C>T, p.Arg673Cys, c.2371A>T, p.Lys791Term) and a known frameshift mutation (c.2554_2557delGAGA, p. Glu852fsTer13). A comprehensive analysis showed that 64.1% (25/39) of the mutant alleles are truncated mutations, and 34.3% (12/39) are missense mutations. About 89.7% (35/39) of the mutations are located in the terminal half of exon 3, which affected the C-terminal of the TOPORS protein. Night blindness was a common onset symptom, and -related ERG changes can be observed in early stage. In addition, patients with missense mutations retained better central vision in older age compared to the patients with truncated mutations.
We expand the mutation spectrum and assess the possible genotype-phenotype correlations of , which can provide a valuable reference for exploring the pathogenesis of adRP caused by mutations.
从我们的患者群体中鉴定出导致视网膜色素变性（RP）的 突变，并总结之前报道的基因型和表型。
从我们的遗传性视网膜病变筛查工作中招募具有 RP 表型的先证者。从外周静脉血中提取 DNA，并进行外显子组测序。我们进一步详细检查了这些患者的临床数据和家族史。从之前的报告中搜索并总结与 RP 相关的 突变，并将结果与我们研究中的数据相结合。系统分析 突变谱，并比较和描述截断突变和错义突变的表型。
在三个家庭中检测到 突变，包括两个新突变（c.2017C>T，p.Arg673Cys，c.2371A>T，p.Lys791Term）和一个已知的移码突变（c.2554_2557delGAGA，p.Glu852fsTer13）。综合分析表明，64.1%（25/39）的突变等位基因是截断突变，34.3%（12/39）是错义突变。大约 89.7%（35/39）的突变位于外显子 3 的末端一半，影响 TOPORS 蛋白的 C 末端。夜盲是常见的首发症状，早期可观察到与 -相关的 ERG 变化。此外，与截断突变相比，携带错义突变的患者在年龄较大时保留了更好的中心视力。
我们扩展了 突变谱，并评估了 突变的可能基因型-表型相关性，这可为探索由 突变引起的常染色体显性 RP 的发病机制提供有价值的参考。
