Variable Expressivity of HNF1B Nephropathy, From Renal Cysts and Diabetes to Medullary Sponge Kidney Through Tubulo-interstitial Kidney Disease

Claudia Izzi, Chiara Dordoni, Laura Econimo, Elisa Delbarba, Francesca Romana Grati, Eva Martin, Cinzia Mazza, Gianfranco Savoldi, Luca Rampoldi, Federico Alberici, Francesco Scolari

Research output: Contribution to journalArticlepeer-review


Introduction: In humans, heterozygous mutations of hepatocyte nuclear factor 1beta (HNF1B) are responsible for a dominant inherited disease with both renal and extrarenal phenotypes. HNF1B nephropathy is the umbrella term that includes the various kidney phenotypes of the disease, ranging from congenital anomalies of the kidney and urinary tract (CAKUT), to tubular transport abnormalities, to chronic tubulointerstitial and cystic renal disease. Methods: We describe 7 families containing 13 patients with ascertained HNF1B nephropathy. All patients underwent genetic testing and clinical, laboratory, and instrumental assessment, including renal imaging and evaluation of extrarenal HNF1B manifestations. Results: Significant inter- and intrafamilial variability of HNF1B nephropathy has been observed. In our cohort, HNF1B pathogenic variants presented with renal cysts and diabetes syndrome (RCAD); renal cystic phenotype mimicking autosomal dominant polycystic kidney disease (ADPKD); autosomal dominant tubulointerstitial kidney disease (ADTKD) with or without hyperuricemia and gout; CAKUT; and nephrogenic diabetes insipidus (NDI). Of note, for the first time, we describe the occurrence of medullary sponge kidney (MSK) in a family harboring the HNF1B whole-gene deletion at chromosome 17q12. Genotype characterization led to the identification of an additional 6 novel HNF1B pathogenic variants, 3 frameshift, 2 missense, and 1 nonsense. Conclusion: HNF1B nephropathy may present with a highly variable renal phenotype in adult patients. We expand the HNF1B renal clinical picture to include MSK as a potential new finding. Finally, we expand the allelic repertoire of the disease by adding novel HNF1B pathogenic variants.

Original languageEnglish
Pages (from-to)2341-2350
Number of pages10
JournalKidney International Reports
Issue number12
Publication statusPublished - Dec 2020


  • cystic kidney disease
  • HNF1B
  • medullary sponge kidney
  • nephrogenic diabetes
  • RCAD
  • tubulointerstitial nephritis

ASJC Scopus subject areas

  • Ophthalmology
  • Nephrology


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