目的:本研究的目的是寻找新的双等位基因CRB1突变,然后从基因型和表型水平对CRB1文献进行分析。
方法:我们筛选了各种变量,例如CRB1突变类型,域,外显子,和基因型及其与特定眼部表型的关系。强调双等位基因错义和无义突变,因为与其他突变类型相比,它们的患病率很高。最后,我们使用多元线性回归模型量化了各种不可改变因素对最佳矫正视力眼(BCVAOU)的影响,并确定了遗传相互作用.
结果:发现CRB1第9外显子中的一种新的双等位基因错义;c.2936G>A;p。(Gly979Asp)与视锥营养不良(RCD)有关。CRB1突变类型,外显子,域,基因型分布根据眼底特征差异显著,如周围色素沉着和状况,光盘,船只,黄斑状况,色素沉着(P<0.05)。在从PubMed检索到的154篇文章中,纳入了96项研究,共439例双等位基因CRB1患者。错义突变与黄斑色素缺失显著相关,苍白的视神经盘,和外围色素沉着,导致RCD的风险更高(P<0.05)。相比之下,纯合无义突变与黄斑色素相关,外围颜料,LCA的风险较高(P<0.05),BCVAOU水平升高。我们发现年龄,突变类型,遗传性视网膜疾病是BCVAOU的关键决定因素,因为它们显着增加了33%26%,38%,分别为(P<0.05)。功能等位基因的丧失增加了LCA的风险,胡说八道比indels有更深远的影响。最后,我们的分析表明p。(Cys948Tyr)和p。(Lys801Ter)和p。(Lys801Ter);p。(Cys896Ter)可能会相互作用以修改BCVAOU水平。
结论:这项荟萃分析更新了文献,并确定了双等位基因CRB1患者的基因型-表型相关性。
OBJECTIVE: The goal of the study was to search for novel bi-allelic CRB1 mutations, and then to analyze the CRB1 literature at the genotypic and phenotypic levels.
METHODS: We screened various variables such as the CRB1 mutation types, domains, exons, and genotypes and their relation with specific ocular phenotypes. An emphasis was given to the bi-allelic missense and nonsense mutations because of their high prevalence compared to other mutation types. Finally, we quantified the effect of various non-modifiable factors over the best-corrected visual acuity oculus uterque (BCVA OU) using multivariate linear regression models and identified genetic interactions.
RESULTS: A novel bi-allelic missense in the exon 9 of CRB1; c.2936G > A; p.(Gly979Asp) was found to be associated with rod-cone dystrophy (RCD). CRB1 mutation type, exons, domains, and genotype distribution varied significantly according to fundus characteristics, such as peripheral pigmentation and condition, optic disc, vessels, macular condition, and pigmentation (P < 0.05). Of the 154 articles retrieved from PubMed, 96 studies with 439 bi-allelic CRB1 patients were included. Missense mutations were significantly associated with an absence of macular pigments, pale optic disc, and periphery pigmentation, resulting in a higher risk of RCD (P < 0.05). In contrast, homozygous nonsense mutations were associated with macular pigments, periphery pigments, and a high risk of LCA (P < 0.05) and increased BCVA OU levels. We found that age, mutation types, and inherited retinal diseases were critical determinants of BCVA OU as they significantly increased it by 33% 26%, and 38%, respectively (P < 0.05). Loss of function alleles additively increased the risk of LCA, with nonsense having a more profound effect than indels. Finally, our analysis showed that p.(Cys948Tyr) and p.(Lys801Ter) and p.(Lys801Ter); p.(Cys896Ter) might interact to modify BCVA OU levels.
CONCLUSIONS: This meta-analysis updated the literature and identified genotype-phenotype associations in bi-allelic CRB1 patients.