Prenatal ultrasound phenotype and genetic analysis of a fetus with renal hypodysplasia/aplasia-3
Objective To analyze the prenatal ultrasound phenotype and genetic features of a fetus with renal hypodysplasia/aplasia-3(RHDA3)due to GREB1L gene mutation.Methods A 25-year-old pregnant woman underwent genetic counseling during pregnancy due to abnormal prenatal ultrasound in the First Affiliated Hospital of Zhengzhou University on February 6,2023.The skin tissue of the aborted fetus and peripheral venous blood of the couple were collected to perform whole exome sequencing,and gene mutation site was retrieved in databases as HGMD,ClinVar,ExAC,1000 Genomes and gnomAD.The pathogenicity of variants was rated with reference to the Criteria and Guidelines for Classification of Genetic Variants and The American College of Medical Genetics and Genomics(ACMG).Uniprot database was used to predict the protein structure of this gene code.The clinical data of the couple and the fetus were collected,and the prenatal ultrasound phenotype and genetic features of the fetus were analyzed.Results One male fetus was induced after genetic counseling.Prenatal ultrasound indicated thickening of the neck and back folds,absence of both kidneys,absence of bladder and amniotic fluid,small magenblase volume and a small amount of pericardial effusion.The fetus carried the frameshift mutation of GREB1L gene c.5429_5442dupGGCC(p.Ile1815fs),and neither parents carried the mutation.This variant has not been reported in the literature,and has not been included in the HGMD and ClinVar databases,which is a noval variant.This mutation led to abnormal amino acid coding and changes in protein function(PVS1).This mutation was not found in ExAC,1000 Genomes and gnomAD databases(PM2_Supporting).The mutation was a novel mutation verified by both parents(PS2).In summary,the mutation was preliminarily determined to be pathogenic(PVS1+PM2_Supporting+PS2).Conclusion The frameset mutation of GREB1L gene c.5429_5442dupGGCC is a noval mutation,which is the genetic cause of RHDA3 type in the fetus of this family,and the main manifestation of prenatal ultrasound is double kidney absence.
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