Multiple diabetes cases and kidney Anomalies in one family

Abstract

Introduction: HNF1B (Hepatocyte Nuclear Factor 1 Beta) is an important transcription factor for the development and functionality of various organs, notably the kidneys and pancreas. Mutations in HNF1B are associated with various clinical phenotypes, including urogenital tract anomalies, monogenic diabetes (MD), abnormal liver function. Diabetes caused by HNF1B defect is very rare, and accounts only <5% of all MD cases. Objectives: Present a family with multiple diabetes cases and kidney anomalies. Methods: Results: We present two siblings, who were followed by pediatric nephrologist because of developmental kidney disease diagnosed antenatally, with no specific treatment. Nevertheless, both children had normal renal function, they were diagnosed with hypomagnesemia and hyperuricemia. In teenage years they were referred to a pediatric endocrinologist after heterozygous variant was found in the HNF1B gene (NM_000458.4:c.[701dupA];[701=]), inducing a frameshift mutation (NP_000449.1:p.[(Asn234fs)];[(Asn234=)]). Glucose profile, C-peptide and insulin of both children were within normal ranges, however, HbA1c had tendency to rise during the follow-up period for 6 months. Analysis of the pedigree showed that the father had diabetes requiring insulin therapy diagnosed from young age, his genetic testingi s still ongoing, his aunt was diagnosed with duplex kidneys. Moreover, both maternal grandparents had diabetes of unknown origin and kidney pathologies. There were more distant relatives from both parental sides with kidney problems and diabetes of unknown origin. Conclusions: The presented case highlights the complexity of HNF1B defects. The varying symptoms observed within the family, such as renal and extra-renal pathologies, confirm a complex genetic landscape. In summary, this case proved the crucial role of genetic testing in cases of congenital anomalies (especially kidney cysts) associated with features as impaired renal transport of electrolytes and/or other substances, and various extra-renal features, as diabetes.