Wnt受体信号通路与严重早产儿视网膜病的关系研究  

A study on the relationship between the Wnt receptor signaling pathway and severe retinopathy of prematurity

作　　者：孙慧清[1] 熊虹[1] 康文清[1] 李明超[1] 余增渊[1] 邢珊[1] 

机构地区：[1]郑州市儿童医院新生儿科,450018

出　　处：《中国新生儿科杂志》2017年第2期91-95,共5页Chinese Journal of Neonatology

基　　金：郑州市2013年度科技发展计划（攻关计划）（20130604）

摘　　要：目的 探讨Wnt受体信号通路与早产儿视网膜病（ROP）的关系.方法 选择2011年1月至2015年6月我院新生儿重症监护病房诊断严重ROP的早产儿为ROP组,同期选取与严重ROP患儿同性别、同胎龄、同日龄的早产儿为对照组.检测两组早产儿血Wnt受体信号通路FZD4、LRP5、ND基因突变情况,进行前瞻性队列研究.结果 共诊断严重ROP患儿32例,纳入对照组29例.两组均未发现ND、FZD4基因突变.26例ROP患儿检测出8种LRP5基因突变,其中7例外显子18错义突变[c.3989C＞T;p.Ala1330Val（rs3736228）];5例外显子8同义突变（c.1647T＞C;p.Phe549Phe）;5例外显子6内含子突变[c.1412＋ 8G＞ A（rs4988319）];3例外显子2错义突变[c.266A＞G;p.Gln89Arg（rs41494349）];2例外显子21内含子突变[c.4349-17C＞T（rs372086596）];2例外显子19同义突变（c.4089C＞T;p.Asp1363Asp）;1例外显子9同义突变（c.1932G ＞A;p.Glu644Glu）;1例外显子16错义突变（c.3580C ＞T;p.Arg1194Cys）.6例对照组患儿检测出3种LRP5基因突变,其中4例外显子8基因同义突变,1例外显子19同义突变,1例外显子9同义突变.ROP组外显子18错义突变和外显子6内含子突变检出率明显高于对照组,差异有统计学意义（P＜0.05）.结论 Wnt受体信号通路的LRP5基因突变可能与早产儿严重ROP的发生相关联.Objective To study the relationship of Wnt receptor signaling pathway and severe retinopathy of prematurity （ROP）.Method From January 2011 to June 2015,preterm infants with severe ROP admitted to the NICU of our hospital were enrolled prospectively.Preterm infants with similar gestational age,gender,and age （in days） admitted to our hospital during the same period were selected as the control group.FZD4,LRP5,and ND gene mutations in Wnt receptor signaling pathway were examined.Result A total of 61 Chinese preterm infants were screened for these three candidate genes of Wnt receptor signaling pathway,32 in ROP group and 29 in control group.ND and FZD4 gene mutations were not found among all cases.Eight types of LRP5 mutations were found in 26 cases of ROP group,including 7 cases of Exon18 missense mutation [c.3989C ＞ T;p.Ala1330Val （rs3736228）],5 cases of Exon8 synonymous mutation （c.1647T ＞ C;p.Phe549Phe）,5 cases of Exon6 intronic mutation [c.1412 ＋ 8G ＞ A （rs4988319）],3 cases of Exon2 missense mutation [c.266A ＞ G;p.Gln89Arg （rs41494349）],2 cases of Exon21 intronic mutation [c.4349-17C ＞ T （rs372086596）],2 cases of Exon19 synonymous mutation （c.4089C ＞ T;p.Asp 1363 Asp）,one case of Exon9 synonymous mutation （c.1 932G ＞ A;p.Glu644Glu）,and one case of Exon16 missense mutation （c.3580C ＞T;p.Arg1194Cys）.Three types of LRP5 mutations were found in 6 cases of the control group,including 4 cases of Exon8 synonymous mutation,one case of Exon19 synonymous mutation,and one case of Exon9 synonymous mutation.The positive rates of Exonl8 missense mutation and Exon6 intronic mutation in severe ROP group were significantly higher than the control group （P ＜ 0.05）.Conclusion LRP5 gene mutations in Wnt receptor signaling pathway may be associated with the occurrence of severe ROP.

关 键 词：WNT信号通路 早产儿视网膜病 基因 

分 类 号：R774.1[医药卫生—眼科]