Meta-analysis Of Gene Mutation Rate Of Norrin/β Catenin Signal Pathway In Familial Exudative Vitreoretinopathy

Research background:Familial exudative vitreoretinopathy（familial exudative vitreoretinopathy,FEVR）is a rare hereditary vitreoretinal disease.FEVR has genetic heterogeneity,including autosomal dominant,autosomal recessive and X-linked recessive inheritance.At present,12 pathogenic genes have been found in FEVR patients,but they still can not explain all cases.Among them,the proteins encoded by NDP,FZD4,LRP5 and TSPAN12 are involved in the Norrin/ β-catenin signal pathway.the four genes of this pathway,had been studied more in FEVR research at present.So far,there are differences in the mutation rates of FEVR-related pathogenic genes in different countries and regions,which suggests that the carrying of FEVR-related pathogenic genes among different ethnic groups may be specific and need further research and analysis.Objective:Through meta analysis,we study the carrying status of four pathogenic genes related to Norrin/ β-catenin signal pathway in familial exudative vitreoretinopathy（familial exudative vitreoretinopathy,FEVR）in different populations,and understand their distribution characteristics,in order to provide some evidence-based medicine for clinical medicine,genetics and health policy-making.Methods:The data about gene detection of familial exudative vitreoretinopathy in Pub Med,Embase,Cochrane,Zhiwang,Wanfang,VIP and CBM were searched comprehensively by computer.After the completion of the retrieval,the literature is screened according to the inclusion and exclusion criteria,and then its quality is evaluated.Finally,the relevant outcome indicators in the selected literature are collated and extracted,and the results are obtained through statistical analysis.The observation index of this study is the mutation rate of the four genes FZD4,NDP,LRP5,TSPAN12.The STATA13.0 statistical software downloaded from the STATA official website was used to process the data and calculate the results of observation indicators for meta analysis.Results:A total of 32 studies were included,including 22 articles on FZD4 gene mutations involving 2219 FEVR probands or patients,16 articles on NDP gene mutations involving 1274 FEVR probands or patients,12 articles on LRP5 gene mutations involving 1084 FEVR probands or patients,and 12 articles on TSPAN12 gene mutations involving 1208 FEVR probands or patients.The final results of Meta analysis are statistically significant,as follows: First,The meta-results of the mutation rate of the whole population: the mutation rate of FZD4 is 13%,the mutation rate of LRP5 is 5%,the mutation rate of LRP5 is 12%,the mutation rate of TSPAN12 is 7%,and the overall mutation rate is 37%.The order of mutation rate was FZD4 > LRP5 >TSPAN12 > NDP.Second,the result analysis of mutation rate of ethnic subgroup: 1.Meta-analysis of the mutation rate of yellow people: the mutation rate of FZD4 is11%,the mutation rate of LDP is 4%,the mutation rate of LRP5 is 12%,the mutation rate of TSPAN12 is 6%,and the overall mutation rate is 33%.The order of mutation rate was LRP5 > FZD4 > TSPAN12 > NDP.2.Meta-analysis of the mutation rate of Caucasians: the mutation rate of FZD4 is 15%,the mutation rate of LDP is 7%,the mutation rate of LRP5 is 15%,the mutation rate of TSPAN12 is 11%,and the overall mutation rate is 49%.The order of mutation rate was LRP5=FZD4 > TSPAN12 >NDP.Third,Analysis of the mutation rate results of the subgroup in the study time: 1.Meta-analysis of the mutation rate before 2015（including 2015）: the mutation rate of FZD4 is 15%,the mutation rate of LRP5 is 5%,the mutation rate of LRP5 is 13%,the mutation rate of TSPAN12 is 9%,the overall mutation rate is 41%,and the mutation rate is FZD4 > LRP5 > TSPAN12 > NDP.2.Meta-analysis of the mutation rate from2016 to 2021: the mutation rate of FZD4 is 11%,the mutation rate of LRP5 is 5%,the mutation rate of TSPAN12 is 12%,and the mutation rate of TSPAN12 is 6%.The overall mutation rate is 34%,and the mutation rate is LRP5 > FZD4 > TSPAN12 >NDP.Conclusion:1.In patients with clinically diagnosed FEVR,the total mutation rate of pathogenic genes related to Norrin/ β-Catenin signaling pathway was 37%,and the mutation rates of FZD4,NDP,LRP5 and TSPAN12 were 13%,5%,12% and 7%respectively.FZD4 is the most common pathogenic gene of FEVR.The above data can be temporarily used as estimated mutation rate of pathogenic genes related to Norrin/ β-Catenin signaling pathway in patients with clinically diagnosed FEVR.2.In patients with clinically diagnosed FEVR,there are ethnic differences in mutation rate.The most common gene mutation in yellow people is LRP5.Whites are more likely to suffer from FEVR,and the most common gene mutations are LRP5 and FZD4.3.In patients with clinical diagnosis of FEVR,the overall mutation rate of studies before 2015（including 2015）is higher than that from 2016 to 2021.The mutation rate of NDP gene is relatively stable,and the mutation rate of the other three genes is significantly lower than that in the past in recent years.It is speculated that the progress of gene testing methods and instruments,the size of samples,and the genetic mode of the disease may affect the detection of mutation rate.