Objective To identify the pathogenic gene of a family with congenital cataract,analyze the relationship be-tween the mutation and abnormal phenotype of the family by phenotype and gene analysis,and provide reference for genetic coun-seling,diagnosis and treatment of the disease family.Methods Collect clinical data of the family members,diagnose their cataract phenotype,draw a family diagram,and analyze their genetic patterns.Whole exome analysis of ectopic sites in proband genome was performed by WES.Screen for deletions/duplications mutation were detected by MPLA test.After excluding the relationship be-tween coding region variation,deletions/duplications mutation with the occurrence of family diseases,the screen of pathogenic genes in this family was completed by WGS.Results 22 members of the family participated in clinical examinations,and 13 members were diagnosed with cataracts,mainly manifested as cortical opacity,nuclear opacity,and unclear fundus vision.The maximum age was 84 years old and the minimum was 11 years old.Analysis of the WES data identified a candidate pathogenic variant in COL7A1 c.6727T＞C,but this variant was not complete co segregation with the phenotype in the pedigree.MLPA results displayed that the deletions/duplications mutation were not existed in RHO,RP1,IMPDH1,PRPF31 gene of this family.Analysis of WGS data identi-fied the FTL c.-168G＞C(rs398124635)variation located in 5'-UTR region of ferritin light chain sub-unit coding gene.Sanger se-quencing demonstrated the heterozygous site was completely co-segregated with the phenotype in the pedigree.Evaluation analysis of Clinvar database suggested it's a harmful variation.Conclusion The genetic mode of this congenital cataract family was auto-somal dominant inheritance,and FTL c.-168G＞C mutation was the pathogenic variation for this congenital cataract family.
维普
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