A New Splicing Mutation c.492+1G>A in the Renin Gene Responsible for Renal Tubular Dysgenesis

Background: The aim of this study was to identify the pathogenicity of Renin (REN) gene candidate renal tubular dysgenesis (RTD) in the aborted fetus.Methods: For suspected pathogenic variants that may cause abnormal RNA splicing, Minigene was used to analyze the effect of the variants on splicing and determine its pathogenicity.Results: Two variants of the REN gene were found in the proband, one was the heterozygous variant c.492+1G>A at the splice site of intron 4, and the other was the heterozygous variant nonsense mutation c.963T>A (p.Y321X) on exon 9. In vitro analysis, Minigene confirmed that the mutation in peGFP-C1 vector resulted in overall retention of intron 4.Conclusion: Our results reported the novel splicing site variation of c.492+1G>A affected the normal mRNA splicing of REN, which was the pathogenic variation leading to RTD.