Signal Peptide Variants in Inherited Retinal Diseases: A Multi-Institutional Case Series.
Signal Peptide Variants in Inherited Retinal Diseases: A Multi-Institutional Case Series.
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DOI：
10.3390/ijms232113361
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发表时间：
2022-11-01
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
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，并在临床基因检测记录的多机构回顾中评估了这些变异的流行率。使用在线数据库RetNet和UniProt来确定哪些IRD基因具有SP。对确诊为IRD和并发SP变异的患者进行了多中心的回顾性研究。在计算机方面，使用MutPred、MutationTaster和信号肽预测工具SignalP6.0进行评估。用SignalP6.0进一步确定每个基因中三个SP区的位置：N-末端区域、疏水核心区域和C-末端区域。目前与IRD相关的56个基因具有SP序列。根据记录回顾，56个拥有SP的基因中总共存在505个变异。根据计算机预测和临床相关性，这些变异中有6个(1.18%)在SP序列内，可能与患者的疾病相关。这6个SP变异体分别位于CRB1(早发性视网膜营养不良)、NDP(家族性渗出性玻璃体视网膜病变)(FEVR)、FZD4(FEVR)、EYS(视网膜色素变性)和RS1(X连锁幼年视网膜劈裂)基因。重要的是要意识到SP突变是IRDS的一种极其罕见的原因。未来的研究将有助于我们更好地了解它们在每一种疾病过程中的作用，并评估治疗方法。
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.
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影响因子：
33.6
作者：
Guerriero CJ;Brodsky JL
通讯作者：
Brodsky JL
影响因子：
3.7
作者：
Lam BL;Leroy BP;Black G;Ong T;Yoon D;Trzupek K
通讯作者：
Trzupek K
影响因子：
4.6
作者：
Hosono K;Nishina S;Yokoi T;Katagiri S;Saitsu H;Kurata K;Miyamichi D;Hikoya A;Mizobuchi K;Nakano T;Minoshima S;Fukami M;Kondo H;Sato M;Hayashi T;Azuma N;Hotta Y
通讯作者：
Hotta Y
影响因子：
17.8
作者：
Berger, Wolfgang;Kloeckener-Gruissem, Barbara;Neidhardt, John
通讯作者：
Neidhardt, John
对1000个遗传性视网膜疾病的连续家庭进行临床焦点分子研究。
影响因子：
13.7
作者：
Stone EM;Andorf JL;Whitmore SS;DeLuca AP;Giacalone JC;Streb LM;Braun TA;Mullins RF;Scheetz TE;Sheffield VC;Tucker BA
通讯作者：
Tucker BA