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
Abstract
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: 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.