Objective To investigate the clinical features and gene variation of a fetus with congenital renal cystic disease.Methods The clinical data of the fetus were collected,and the genetic analysis of the fetus and its parents was per-formed by chromosome karyotype analysis,low depth whole genome sequencing copy number variation detection(CNV-seq)and trio-whole exome sequencing(trio-WES).The candidate variant was verified by Sanger sequencing.Bioinformatics tools were used to evaluate the conservation of amino acids,to analyze the structural changes of proteins,and to predict the patho-genicity of mutant protein.Results Detailed fetal ultrasonic examination had revealed bilateral renal cysts.Karyotype analysis did not detect abnormalities in chromosome number or structure.The CNV-seq test did not detect aneuploidy or pathogenic copy number variation associated with fetal phenotype.Trio-WES found that the fetus carried a frameshift mutation of HNF1B NM_000458.2:c.1120dupA(p.Met374Asnfs*26),which was verified by Sanger sequencing as a novel mutation.The mutant amino acid was highly conserved in multiple species,and the mutant HNF1B protein structure was damaged.The key domain of the tail is missing.Combined with the results of fetal clinical phenotype and genetic testing,the diagnosis of autosomal dominant HNF1B-associated kidney disease caused by novel mutation of HNF1B gene was considered.Conclusion The de novo frameshift mutation of HNF1B c.1120dupA is the genetic cause of fetal multiple renal cysts and has an important role in predicting the postnatal phenotype.This study enriched the pathogenic variation spectrum of HNF1B gene.
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