Abstract：
Signal peptide (SP) mutations are an infrequent cause of inherited retinal diseases (IRDs). We report the genes currently associated with an IRD that possess an SP sequence and assess the prevalence of these variants in a multi-institutional retrospective review of clinical genetic testing records. The online databases, RetNet and UniProt, were used to determine which IRD genes possess a SP. A multicenter retrospective review was performed to retrieve cases of patients with a confirmed diagnosis of an IRD and a concurrent SP variant. In silico evaluations were performed with MutPred, MutationTaster, and the signal peptide prediction tool, SignalP 6.0. SignalP 6.0 was further used to determine the locations of the three SP regions in each gene: the N-terminal region, hydrophobic core, and C-terminal region. Fifty-six (56) genes currently associated with an IRD possess a SP sequence. Based on the records review, a total of 505 variants were present in the 56 SP-possessing genes. Six (1.18%) of these variants were within the SP sequence and likely associated with the patients\' disease based on in silico predictions and clinical correlation. These six SP variants were in the CRB1 (early-onset retinal dystrophy), NDP (familial exudative vitreoretinopathy) (FEVR), FZD4 (FEVR), EYS (retinitis pigmentosa), and RS1 (X-linked juvenile retinoschisis) genes. It is important to be aware of SP mutations as an exceedingly rare cause of IRDs. Future studies will help refine our understanding of their role in each disease process and assess therapeutic approaches.
摘要：
信号肽(SP)突变是遗传性视网膜疾病(IRD)的罕见原因。我们报告了目前与具有SP序列的IRD相关的基因，并在对临床基因检测记录的多机构回顾性审查中评估了这些变异的患病率。在线数据库，RetNet和UniProt，用于确定哪些IRD基因具有SP。进行了多中心回顾性审查，以检索确诊为IRD和并发SP变异的患者病例。使用MutPred进行了计算机模拟评估，MutationTaster,和信号肽预测工具，信号6.0。SignalP6.0进一步用于确定每个基因中三个SP区域的位置：N末端区域，疏水核心，和C端区域。目前与IRD相关的56个基因具有SP序列。根据记录审查，共有505个变异体存在于56个具有SP的基因中.根据计算机预测和临床相关性，这些变异中有六个（1.18％）在SP序列内，可能与患者疾病相关。这六个SP变异在CRB1（早发性视网膜营养不良）中，NDP（家族性渗出性玻璃体视网膜病变）（FEVR），FZD4(FEVR),EYS（色素性视网膜炎），和RS1（X连锁的青少年视网膜裂）基因。重要的是要意识到SP突变是IRD的极其罕见的原因。未来的研究将有助于完善我们对它们在每种疾病过程中的作用的理解，并评估治疗方法。
