title: A new mutation in the hepatocyte nuclear factor-1-alpha gene (P224S) in a newly discovered German family with maturity-onset diabetes of the young 3 (MODY 3). Family members carry additionally the homozygous I27L amino acid polymorphism in the HNF1 alpha gene.
abstract: Mutations in the hepatocyte nuclear factor-1-alpha gene cause maturity onset diabetes of the young 3 (MODY 3). Here we describe a new family affected by this disorder carrying the so far unknown mutation Pro224Ser in exon 3. First we identified a 17-year-old patient. OGTT demonstrated that insulin secretion was severely impaired: basal insulin was 3.7 uU/ml and 60 min after an oral glucose load plasma insulin peaked only threefold to 10.7 uU/ml. In addition, this patient carries the homozygous polymorphism Ile27Leu (exon1) in the hepatocyte nuclear factor-1-alpha gene that was shown to be associated with insulin resistance. So far, we have no evidence for insulin resistance in this individual patient. Additionally, two other family members carry the hepatocyte nuclear factor-1-alpha mutation Pro224Ser and the homozygous polymorphism Ile27Leu. A similar case with these two mutations in the HNF-1-alpha gene has not been described before. This data will allow to discover more patients with MODY 3.
authors.affiliation: Practice for Internal Medicine and Diabetes, Marburg, Germany.
authors.forename: H-C
authors.initials: HC
authors.lastname: Fehmann
authors.forename: U
authors.initials: U
authors.lastname: Gross
authors.forename: M
authors.initials: M
authors.lastname: Epe
mesh_terms: D000293:Adolescent; D000368:Aged; D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005091:Exons; D005260:Female; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D006720:Homozygote; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D007532:Isoleucine; D007930:Leucine; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D011392:Proline; D012694:Serine; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D007532:Isoleucine; D051537:Hepatocyte Nuclear Factor 1; D012694:Serine; D011392:Proline; D007930:Leucine