Mutations in the diabetes susceptibility genes hepatocyte nuclear factor (HNF) 1 alpha (α), HNF1β and HNF4α

A method for detecting whether a human has or has a propensity for a MODY diabetic disease state indicated by the presence or absence of a mutation in an HNF1α gene, an HNF4α gene, or an HNF1β gene of the human, said method comprising:

• a) obtaining sample nucleic acid from a human;
• and
• b) analyzing the sample nucleic acid to detect a mutation in an HNF-encoding nucleic acid segment, wherein the mutation in an HNF-encoding nucleic acid segment is (I) a mutation which results in a change in the amino acid sequence of an HNF encoded polypeptide different from wildtype, or (ii) a mutation selected from the group consisting of a truncation, a substitution, a frameshift, a mutation which results in differential splicing of the HNF gene, and a mutation in the promoter region of the HNF gene, such that the expression or activity of the HNF encoded polypeptide is reduced or eliminated, and wherein the HNF-encoding nucleic acid segment is further defined as an HNF1α-encoding nucleic acid segment, an HNF4α-encoding nucleic acid segment, or an HNF1β-encoding nucleic acid segment;
• wherein the mutation in the HNF-encoding nucleic acid segment is indicative of the human having a MODY diabetic disease state or having a propensity for a MODY diabetic disease state indicated by a mutation in an HNF1α gene, an HNF4α gene, or an HNF1β gene of the human.