重庆地区家族性渗出性玻璃体视网膜病变患儿FZD4基因突变情况调查分析  

Investigation and analysis of FZD4 gene mutations in paediatric patients with familial exudative vitreoretinopathy in Chongqing area

作　　者：周文轲 何俐莹[1] 陶雪莹 岑超 龚立艳 黎琦 李春梅 刘娅 ZHOU Wenke;HE Liying;TAO Xueying;CEN Chao;GONG Liyan;LI Qi;LI Chunmei;LIU Ya(Department of Eye and Otorhinolaryngology,Chongqing Health Center for Women and Children(Women and Children′s Hospital of Chongqing Medical University),Chongqing 400000,China)

机构地区：[1]重庆市妇幼保健院(重庆医科大学附属妇女儿童医院)眼耳鼻喉科,重庆400000

出　　处：《中国临床新医学》2024年第8期871-874,共4页CHINESE JOURNAL OF NEW CLINICAL MEDICINE

基　　金：重庆市社会事业与民生保障科技创新专项重点研发资助项目(编号:cstc2017shms-zdyfX0049)。

摘　　要：目的 调查分析重庆地区家族性渗出性玻璃体视网膜病变(FEVR)患儿FZD4基因的突变情况,并分析基因型与表型的关联性。方法 招募2019年1月至2022年12月重庆市妇幼保健院经新生儿眼病筛查诊断为FEVR的患儿90个家系(300例),均来自重庆地区。所有患儿均采用RetCamⅢ广域眼底成像系统行眼底检查,并通过RNA-seq高通量测序对白细胞基因组DNA进行FZD4、NDP、LRP5、TSPAN12、ZNF408、CFTR、ADGRG2、SLC9A3、KIF11、CAPN5等10个FEVR致病基因进行检测。分析患者基因型与表型的关联性。结果 90例先证者中,检出FZD4基因突变4例(4.44%),其中2例为自发性突变,2例为父源性突变,突变类型均为非同义突变。4例患儿均为双眼发病,根据FEVR分期,1期3眼,2A期3眼,2B期2眼;根据FEVR分区,2区2眼,3区6眼。合并CAPN5基因突变1例。该研究发现的染色体突变位置包括chr11-86662209、chr11-86663485、chr11-86665923、chr11-86662893。结论 该研究拓展了FZD4基因的突变频谱,证实FEVR患者的基因型与表型可能存在不一致的情况。Objective To investigate and analyze FZD4 gene mutations in paediatric patients with familial exudative vitreoretinopathy(FEVR)in Chongqing area,and to analyze the relationship between genotype and phenotype.Methods A total of 90 pedigrees(300 cases)of the paediatric patients who were diagnosed with FEVR after neonatal eye disease screening in Chongqing Health Center for Women and Children from January 2019 to December 2022 were recruited.All the members of the 90 pedigrees came from Chongqing area.All the paediatric patients underwent fundus examination by using wide-field fundus imaging system of RetCamⅢ,and 10 pathogenic genes of FEVR(including FZD4,NDP,LRP5,TSPAN12,ZNF408,CFTR,ADGRG2,SLC9A3,KIF11 and CAPN5)were detected in the genomic DNA of leukocytes by high-throughput RNA sequencing(RNA-Seq).The relationship between genotype and phenotype in the patients was analyzed.Results Among the 90 probands,4 cases(4.44%)were found to have FZD4 gene mutations,including 2 cases of spontaneous mutations and 2 cases of paternal source mutations,and these types of mutations were non-synonymous mutations.All the 4 paediatric patients had binocular diseases.According to FEVR staging,3 eyes were in stage 1,3 eyes in stage 2A and 2 eyes in stage 2B.According to FEVR zoning,2 eyes were located in zone 2 and 6 eyes in zone 3.There was 1 case in combination with CAPN5 gene mutation.The chromosomal mutation sites discovered in this study included chr11-86662209,chr11-86663485,chr11-86665923 and chr11-86662893.Conclusion This study expands the mutation spectrum of FZD4 gene and confirms that there may be inconsistency between geno-type and phenotype in patients with FEVR.

关 键 词：家族性渗出性玻璃体视网膜病变 FZD4基因 重庆 

分 类 号：R779.7[医药卫生—眼科]