title: Atypical phenotypic features among carriers of a novel Q248X nonsense mutation in the HNF1B gene.
abstract: BACKGROUND
  Hepatocyte transforming factor 1B-maturity onset diabetes mellitus of the young (HNF1B-MODY) is an autosomal dominant type of monogenic diabetes caused by a mutation in the gene encoding hepatocyte nuclear factor 1beta (HNF-1beta). The aim of this study was to determine if a HNF1B gene mutation was responsible for a dominantly inherited form of diabetes mellitus among the members of a three-generation Polish family.
  
  
  METHODS
  The index subject was a 13-year-old boy with metabolic syndrome, spina bifida occulta, posterior urethral valves, congenital ureteropelvic junction obstruction, and a family history of diabetes of autosomal dominant trait of inheritance. We performed clinical and laboratory examinations of his family and sequenced the HNF1B gene.
  
  
  RESULTS
  A novel Q248X mutation (nucleotide C to T transition at position 742 of the exon 3 of HNF1B gene, resulting in stop codon formation) was identified. Phenotypes of family members sharing this mutation are highly variable, and include previously known abnormalities of the urinary system and pancreas, diabetes mellitus of variable onset and severity, hyperinsulinaemia, insulin resistance, metabolic syndrome, elevated aminotransferases, hyperbilirubinemia, hyperamylasemia, short stature and cataracts. To the best of our knowledge, spina bifida occulta, pectus carinatum, and splenomegaly have not been previously reported.
  
  
  CONCLUSIONS
  Our results broaden the spectrum of HNF1B gene mutations and HNF1B-MODY-related phenotypes.
authors.affiliation: Department of Paediatrics, Oncology, Haematology and Diabetology, Medical University of Lodz, Poland. anna.hogendorf@umed.lodz.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Hogendorf
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Kosińska-Urbańska
authors.forename: Maciej
authors.initials: M
authors.lastname: Borowiec
authors.forename: Karolina
authors.initials: K
authors.lastname: Antosik
authors.forename: Krystyna
authors.initials: K
authors.lastname: Wyka
authors.forename: Wojciech
authors.initials: W
authors.lastname: Młynarski
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics*; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D016136:Spina Bifida Occulta / Q000150:complications / Q000235:genetics*; D014517:Ureteral Obstruction / Q000150:complications / Q000235:genetics*
chemical_list: D051539:Hepatocyte Nuclear Factor 1-beta