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

ZHOU Wenke; HE Liying; TAO Xueying; CEN Chao; GONG Liyan; LI Qi; LI Chunmei; LIU Ya

doi:10.3969/j.issn.1674-3806.2024.08.06

Abstract：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,TSP AN 12,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.