An interesting unfolding of the diagnosis of hepatocyte nuclear factor-1 beta (HNF1β) monogenic diabetes

Abstract

The HNF1B gene plays an important role in endodermal development, and mutations of HNF1B are associated with the renal cysts and diabetes (RCAD) syndrome. Other than renal cystic malformations and monogenic diabetes, various other abnormalities have been described depending on HNF1β expression. Molecular diagnosis has huge implications for the treatment of the patient and their family members. We present a case of RCAD syndrome with a previously unreported mutation. A 49-year-old man with diabetes mellitus was admitted with worsening chronic kidney disease requiring haemodialysis. He developed recurrent, unexplained hypoglycaemia despite discontinuing insulin, making the diagnosis of type 1 diabetes mellitus questionable. He had detectable serum C-peptide (742 pmol/L), and anti-GAD and anti-pancreatic islet cell antibodies were negative. Abdominal imaging revealed renal cortical cysts and atrophic pancreas. A significant family history of diabetes mellitus with renal disease was also established which prompted us to suspect mutation of the HNF1B gene. Genetic testing confirmed the diagnosis: he was found to have a novel HNF1B missense mutation p.R165C previously not reported. This case study identified a mutation previously unreported thereby expanding the spectrum of HNF1B gene mutations. Copyright © 2017 John Wiley & Sons.