双胞胎早产儿视网膜病变与NDP/FZD4基因相关分析

Correlation Analysis between Retinopathy of Prematurity in Twins and the NDP/FZD4 Gene

目的:评估及验证中国人双胞胎早产儿视网膜病变(ROP)是否与NDP和FZD4基因突变有关。方法:系列病例研究。收集2017年1-12月在上海市儿童医院的6对12例双胞胎ROP3期患儿,平均胎龄为31周,平均出生体质量为1252g,均为出生后4~6周,进行临床及基因检查,通过外周血人基因组DNA提取,采用聚合酶链式反应(PCR)扩增及Sanger测序。结果:12例双胞胎早产儿ROP3期患儿中6例诊断阈值病变后立即转外院进行光凝联合眼内抗血管内皮生长因子(VEGF)注药治疗,另6例经过门诊密切随访均自行恢复并消退,其中最长随访期达患儿出生后7个月之久。研究中所有患儿的NDP和FZD4基因均未检测到明确的致病性点突变或小的序列插入/缺失。结论:未发现双胞胎早产儿ROP与NDP、FZD4基因的突变相关,分析可能与其他基因或种族因素相关。

Objective:To evaluate and verify the correlation between retinopathy of prematurity(ROP)in preterm infant Chinese twins with the NDP/FZD4 gene mutation.Methods:In this case series study,clinical evaluations and gene examinations were done on 12 cases of preterm infant twins(6 couples,aged 4-6 weeks)with ROP which were identified in Shanghai Children's Hospital from January 2017 to December 2017.The mean gestation age was 31 weeks and the mean weight was 1 252 g.Polymerase chain reaction(PCR)amplification and Sanger sequencing were used to extract the human genome DNA from peripheral blood.Results:Twelve premature infants were diagnosed with stage 3 ROP,and 6 infants were diagnosed with threshold ROP disease and treated with photocoagulation combined with an injection of intraocular anti-VEGF medication.Lesions in the other 6 infants subsided during the follow-up period.The longest follow-up period was 7 months after birth.Neither a clear pathogenicity point mutation nor a small insertion/deletion in either a NDP or FZD4 gene was detected in any infants in the study.Conclusions:There was no mutation correlation with the NDP or FZD4 gene in ROP in preterm infant twins.We predicate that other genetic or racial factors cause the ROP in preterm infant twins.