A Case of a Novel HNF1B Gene Mutation (c.316C>T) and the Renal and Extra-Renal Manifestations of HNF1B Nephropathy

Hepatocyte nuclear factor 1-beta (HNF1B), located on chromosome 17q12, plays a critical role in the embryonic development of the kidneys, pancreas, liver, and genital tract. HNF1B has a heterozygous mutation that is also associated with neurodevelopmental diseases. Here, we describe the case of a female infant with bilateral renal enlargement and multiple cysts detected on prenatal ultrasonography. Postnatal imaging confirmed these findings and laboratory evaluation revealed transient hyperuricemia without hypomagnesemia or elevated liver enzyme levels. Targeted next-generation sequencing identified a novel heterozygous nonsense variant in the Pit-Oct-Unc-specific domain of HNF1B (c.316C>T; p.Gln106Ter), which was predicted to introduce a premature stop codon at amino acid position 106. As the patient grew older, the risk of developmental delays increased. This case illustrates the broad phenotypic spectrum of HNF1B-associated nephropathy and emphasizes the importance of HNF1B analysis in neonates presenting with renal and extra-renal manifestations. Early identification of HNF1B mutations facilitates the appropriate monitoring and management of symptoms, including neurodevelopmental outcomes. Further studies are needed to elucidate genotype-phenotype correlations and expand our understanding of HNF1B-related disorders.