title: Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in maturity-onset diabetes of the young.
abstract: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset (often <25 years of age), and pancreatic beta-cell dysfunction. MODY is both clinically and genetically heterogeneous, with six different genes identified to date; glucokinase (GCK), hepatocyte nuclear factor-1 alpha (HNF1A, or TCF1), hepatocyte nuclear factor-4 alpha (HNF4A), insulin promoter factor-1 (IPF1 or PDX1), hepatocyte nuclear factor-1 beta (HNF1B or TCF2), and neurogenic differentiation 1 (NEUROD1). Mutations in the HNF1A gene are a common cause of MODY in the majority of populations studied. A total of 193 different mutations have been described in 373 families. The most common mutation is Pro291fs (P291fsinsC) in the polycytosine (poly C) tract of exon 4, which has been reported in 65 families. HNF4A mutations are rarer; 31 mutations reported in 40 families. Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. The identification of an HNF1A or 4A gene mutation confirms a diagnosis of MODY and has important implications for clinical management.
authors.affiliation: Department of Molecular Genetics, Royal Devon & Exeter NHS Foundation Trust, Exeter, United Kingdom. S.Ellard@exeter.ac.uk
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Kevin
authors.initials: K
authors.lastname: Colclough
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D003937:Diagnosis, Differential; D005820:Genetic Testing; D005838:Genotype; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D051557:Hepatocyte Nuclear Factor 4 / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D013453:Sulfonylurea Compounds / Q000627:therapeutic use
chemical_list: C496592:HNF4A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D013453:Sulfonylurea Compounds