title: Divergent phenotypes in siblings with identical novel mutations in the HNF-1α gene leading to maturity onset diabetes of the young type 3.
abstract: BACKGROUND
  Maturity onset diabetes of the young (MODY) is an autosomal dominant form of non-insulin-dependent diabetes mellitus caused by mutations in at least 13 different genes. The hepatocyte nuclear factor (HNF)-1α gene is affected in the most common form (HNF1A-MODY [MODY3]).
  
  
  METHODS
  We describe the co-inheritance of a novel heterozygous missense mutation c.1761C > G (p.Pro588Ala) with a novel complex deletion insertion mutation (c.1765_1766delinsGCCCGfs86*) in the HNF-1α gene among affected members of one family. Both mutations were present in the affected patients and neither was present in unaffected family members. The family had not only inheritance of MODY but also increased susceptibility to type 2 diabetes. Therefore one family member had classical type 2 diabetes including metabolic syndrome aggravated by a genetic predisposition in the form of HNF1A-MODY.
  
  
  CONCLUSIONS
  The presence of common type 2 diabetes features should not detract from the possibility of MODY in patients with a striking autosomal-dominant family history.
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center at the Heinrich-Heine-University Duesseldorf, Leibniz Center for Diabetes Research, Duesseldorf, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Knebel
authors.affiliation: Institute for Diabetes Research, Department of General Internal Medicine, Asklepios Clinic St. Georg, Asklepios Campus Hamburg, Medical Faculty of Semmelweis University, Hamburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Mack
authors.affiliation: Institute for Diabetes Research, Department of General Internal Medicine, Asklepios Clinic St. Georg, Asklepios Campus Hamburg, Medical Faculty of Semmelweis University, Hamburg, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Haas
authors.affiliation: Institute for Diabetes Research, Department of General Internal Medicine, Asklepios Clinic St. Georg, Asklepios Campus Hamburg, Medical Faculty of Semmelweis University, Hamburg, Germany.
authors.forename: Mona Kathrin
authors.initials: MK
authors.lastname: Herman-Friede
authors.affiliation: Institute for Diabetes Research, Department of General Internal Medicine, Asklepios Clinic St. Georg, Asklepios Campus Hamburg, Medical Faculty of Semmelweis University, Hamburg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Lange
authors.affiliation: Diabetes Care Center Buxtehude, Buxtehude, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Schubert
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center at the Heinrich-Heine-University Duesseldorf, Leibniz Center for Diabetes Research, Duesseldorf, Germany.
authors.forename: Jorg
authors.initials: J
authors.lastname: Kotzka
authors.affiliation: Institute for Diabetes Research, Department of General Internal Medicine, Asklepios Clinic St. Georg, Asklepios Campus Hamburg, Medical Faculty of Semmelweis University, Hamburg, Germany. d.mueller-wieland@asklepios.com.
authors.forename: Dirk
authors.initials: D
authors.lastname: Muller-Wieland
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha
keywords: HNF-1α; HNF1A-MODY; Maturity-onset diabetes of the young; Metabolic challenge; Metabolic syndrome; Phenotype variety