Whole exome sequencing is increasingly used to identify disease-causing gene mutations. We used this method to determine the genetic basis of a syndrome of diabetes and renal disease affecting a mother and her son. We identified a mutation in the hepatocyte nuclear factor 1-b (HNF1B) gene that encoded a methionine to valine amino acid change at position 160 (M160V). This knowledge enabled the previously unappreciated diagnosis of maturity-onset diabetes of the young type 5 (MODY5) and provided a basis for genetic counseling for other family members.
This case will provide a basis for reviewing monogenic diabetes syndromes that present in adulthood. The clinical utility of the new genome sequencing methods will also be discussed.