title: Proposed mechanism for a novel insertion/deletion frameshift mutation (I414G415ATCG-->CCA) in the hepatocyte nuclear factor 1 alpha (HNF-1 alpha) gene which causes maturity-onset diabetes of the young (MODY).
abstract: Maturity-onset diabetes of the young (MODY) is a monogenic subgroup of non-insulin dependent diabetes (NIDDM) characterized by an early age of diagnosis (usually < 25 years) and an autosomal dominant mode of inheritance. Mutations in the hepatocyte nuclear factor 1 alpha (HNF-1alpha) [MODY3] gene represent the most common cause of MODY in the UK and a common cause of MODY in many other populations. Sixty-three different mutations have been described in a total of 112 families worldwide. This report describes two families, not known to be related, who carry a novel insertion/deletion mutation (I414G415ATCG-->CCA) and a 6bp intronic deletion of the HNF-1alpha gene in cis. We propose that the insertion/deletion mutation has arisen by formation of a hairpin loop due to the presence of a quasi-palindromic sequence, followed by insertion of CC and deletion of TCG resulting in the increased stability of the hairpin loop.
authors.affiliation: Department of Vascular Medicine and Diabetes Research, School of Postgraduate Medicine and Health Sciences, University of Exeter, UK.
authors.forename: S
authors.initials: S
authors.lastname: Ellard
authors.forename: M P
authors.initials: MP
authors.lastname: Bulman
authors.forename: T M
authors.initials: TM
authors.lastname: Frayling
authors.forename: M
authors.initials: M
authors.lastname: Shepherd
authors.forename: A T
authors.initials: AT
authors.lastname: Hattersley
mesh_terms: D000328:Adult; D001483:Base Sequence; D004268:DNA-Binding Proteins; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics*; D009687:Nuclear Proteins; D010375:Pedigree; D017384:Sequence Deletion / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta