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

Abstract

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The Varied Clinical Presentation of Autosomal Dominant Tubulointerstitial Kidney Disease Due to HNF1β Mutations

“…As described by Izzi et al. , 2 mutations in HNF1β are truly a great masquerader, presenting with signs and symptoms that could be ascribed to many other nephrologic conditions. Making diagnosis even more difficult, there are frequently de novo mutations.…”

“…The allelic heterogeneity is reflected by the varied clinical presentation, making diagnosis difficult. In this month’s Kidney International Reports , Izzi and colleagues 2 present a case series showing the many presentations of HNF1β mutations, including a newly described manifestation: medullary sponge kidney.…”

“…Patients may present with no cysts, a few cysts, or many cysts in the kidney, as in Family 1 in the article by Izzi et al. 2 …”

“…S1 An HNF1β mutation provides a unifying diagnosis for many mysterious and seemingly unrelated conditions. For example, in Family 1, 2 polycystic kidneys, hypomagnesemia, hypokalemia, diabetes, and pancreatic hypoplasia were all found due to an HNF1β mutation. Diagnoses will help prevent unneeded kidney biopsies.…”

Hepatocyte nuclear factors play an important role in the pathogenesis of nephropathy

“…Moreover, Hnf1b knockout in mice led to a polycystic phenotype and Hnf1b mutations in zebrafish affected pronephros development leading to cystic pronephric tubules 7 . In humans, heterozygous mutations in HNF1B are associated with maturity‐onset of diabetes of the young type 5 (MODY5), renal cysts and diabetes syndrome, and with diverse forms of non‐diabetic nephropathies, including autosomal dominant tubulointerstitial kidney disease, autosomal dominant polycystic kidney disease and medullary sponge kidney 8 . The renal manifestations include cystic renal dysplasia, probably due to defective nephrogenesis, oligomeganephronia and glomerulocystic kidney disease.…”