Clinical And Genetic Susceptibility Research Of Retinopathy Of Prematurity (ROP)

Objective The aim of the study were to determine the incidence and evolution of retinopathy of prematurity(ROP)and evaluate possible risk factors associated with the development of ROP among premature infants in Tianjin,Gene sequencing technology was applied to some infants,in order to estimate the effect of candidate gene.Several cases of FEVR was collected to be analysed by Gene sequencing technology.The connection and differentiation was discussed between the cases of FEVR and ROP.Methods 1.A multicentre retrospective review was undertaken of the records of 2492preterm infants in several hospitals of Tianjin,during the period 2008-2013.Data were extracted and analysed only in those patients who were born on 37 or less weeks of gestational age.Screening criteria were established basing on the ROP screening guidelines.The presentation and evolution of ROP have been investigated,and the characteristics associated with ROP in neonates and infants have been also described.Blood samples were collected on the parts of the babys who were be stable status and DNA were extraction from peripheral blood.Suspected mutation were discovered by using high-throughput gene sequencing technology.FZD4,LRP5,TSPAN12 and NDP were candidate gene that come from familial exudative vitreoretinopathy(FEVR).The same gene sequencing of the four candidate genes were also carried out in FEVR patients.Results Retinopathy of prematurity was detected in 7.6%of 2559 neonates who had eye examinations.In normal group the mean gestation age and the mean birth weight was31.87±2.36w and 1709.04±471.05g respectively,which were higher than ROP group(the mean gestation age was 29.41±2.34w and the mean birth weight was 1336.98±408.31g),difference was statistically significant(gestation age Z=-12.72,P<0.01;birth weight Z=-11.19,P<0.01).Duration of supplemental oxygen of infants in normal and ROP group were 41.5%and 63.4%respectively,difference was statistically significant(χ2=35.127,P<0.01).Multiple logistic regression analyses for ROP indicated that low birth weight,young gestational age and duration of ventilation were risk factors for development of ROP.2.The results of gene sequencing 2.1 Eleven synonymous mutation were found on LRP5 gene.Three of which were novel,including c.121C>A,p.R41R,c.4311C>T,p.F1437F,c.4592G>C,p.P1495P.2.2 Two missense mutation of LRP5 were c.266A>G,p.Q89R and c.3989C>T,p.A1330V.2.3 A novel missense mutation was found on TSPAN 12gene.No abnormal change was discovered in 50 healthy person.Evaluated by Polyphen2 and Sift software,the mutation had little effect on protein function,2.4 No mutations change were found of FZD4 and NDP in this study.2.5 A heterozygous change occurs on exon 6(c.1330C,T,p.R444C)inⅠ:land Ⅱ:1 members of LW family.Conclusion 1.The incidence of ROP among premature infants in Tianjin was 7.6%.Low birth weight,young gestational age and duration of ventilation were associated with the development of ROP.The aim is that prevent the occurrence of serious complications,to provide reference for the prevention of premature infants.2.The novel mutation on TSPAN12(c.954G>A)was account for 3.33%(1/30)of ROP patients,3.Most of mutations on LRP5 are single nucleotide polymorphism which is not pathogenicity in this study,4.New missense mutation of TSPAN12 gene has little effect on the protein function,5.The mutation discovered in FEVR family is one of pathogenic gene have been found,indicating the correlation with the onset of LRP gene and FEVR 6.FEVR is a hereditary disorder and ROP is caused by multiple factors.Genetic mutations can only explain a small proportion of the ROP population,suggesting that the formation of other sites of NDP,FZD4,LRP5 and TSPAN12 gene or not found in genes involved in the pathogenesis of ROP.