Maturity-onset diabetes of the young and hepatic adenomatosis - Characterisation of a new mutation

K. A. Iwen, J. Klein, C. Hubold, H. Lehnert, J. M. Weitzel*

*Corresponding author for this work
4 Citations (Scopus)


Aim: Hepatocyte nuclear factor 1 alpha (HNF1A) mutations cause maturity-onset diabetes of the young (MODY) type 3. Further extending the phenotypic spectrum, HNF1A mutations are associated with hepatic adenomatosis. A 20-year old lean, female patient with newly diagnosed diabetes mellitus was negative for diabetes-associated autoantibodies and had no relevant family history. Hepatic adenomatosis was diagnosed. Her HNF1A gene was examined and identified alterations further analysed. Methods & Results: Sequencing of her HNF1A gene revealed a previously uncharacterised Q495X nonsense mutation, along with the known A98V polymorphism, both in the heterozygous state. The patient's father was also a carrier of both the mutation and the polymorphism. An oral glucose tolerance test (OGTT) revealed impaired glucose tolerance, whereas imaging of his liver was unremarkable. Wild type HNF1A and HNF1A carrying the Q495X mutation were co-transfected in reporter gene assays. The mutation causes a dominant-negative HNF1A protein variant which blocks HNF1A wild-type-mediated gene expression. Conclusion: The novel Q495X mutation is the likely cause of our patient's diabetes and hepatic adenomatosis. It may also cause her father's impaired glucose tolerance. More generally speaking, if non-autoimmune diabetes is suspected, examination of the liver may provide important diagnostic clues. Furthermore, patients with hepatic adenomatosis without known diabetes should be screened by OGTT. Relatives of patients with HNF1A mutations should also be screened by OGTT to detect potential early-stage diabetes.

Original languageEnglish
JournalExperimental and Clinical Endocrinology and Diabetes
Issue number6
Pages (from-to)368-371
Number of pages4
Publication statusPublished - 29.04.2013

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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