HNF1B – Unilateral Multicystic Dysplastic Kidney

HNF1B is a POU-homeodomain transcription factor whose heterozygous loss-of-function causes congenital anomalies of the kidney and urinary tract. In a cohort of Japanese patients with renal hypodysplasia and unilateral multicystic dysplastic kidney (MCDK), HNF1B alterations were identified in 5 of 50 individuals (10%) (PMID:20155289). Three probands with unilateral MCDK harbored de novo heterozygous complete gene deletions spanning HNF1B, two of which exhibited contralateral hypodysplasia and one a normal contralateral kidney, illustrating variable expressivity (PMID:20155289). Additional probands with bilateral hypodysplasia carried a novel truncating frameshift and a missense variant c.226G>T (p.Gly76Cys) (PMID:20155289).

Mechanistic studies demonstrate that HNF1B haploinsufficiency disrupts pronephric development: expression of HNF1B mutants in Xenopus embryos yields pronephros agenesis or hypoplasia consistent with human phenotypes (PMID:10758154). Collectively, genetic and functional evidence support a limited but actionable association between HNF1B and unilateral MCDK. Clinical testing of HNF1B in unexplained MCDK cases facilitates accurate diagnosis, informs surveillance for multisystem involvement, and guides family counseling.

References

• Pediatric nephrology • 2010 • HNF1B alterations associated with congenital anomalies of the kidney and urinary tract. PMID:20155289
• Proceedings of the National Academy of Sciences of the United States of America • 2000 • The mutated human gene encoding hepatocyte nuclear factor 1beta inhibits kidney formation in developing Xenopus embryos. PMID:10758154

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