title: Wolfram syndrome in the Polish population: novel mutations and genotype-phenotype correlation.
abstract: OBJECTIVE
  Wolfram syndrome is a rare form of diabetes mellitus associated with optic atrophy and disorders of different organs (e.g. diabetes insipidus, hearing loss, ataxia, anaemia and many others). This syndrome is caused by recessive mutations in the wolframin gene (WFS1) localized on chromosome 4p16·1. The aim of this study was to identify the causative mutations in WFS1 in a group of Polish patients with suspected Wolfram syndrome.
  
  
  METHODS
  
  
  
  METHODS
  Nine patients with clinical symptoms consistent with Wolfram syndrome (at least diabetes mellitus and optic atrophy) and 22 first-degree relatives were examined. The molecular analysis was carried out by direct sequencing of the exons, the exon-intron junctions, and the 5' and 3' untranslated regions of WFS1.
  
  
  RESULTS
  Nine different mutations in WFS1 (five of them novel) were identified in the nine patients. Six patients were homozygous for the following mutations: V412fs, S443R, W539X, V659fs. They developed diabetes at a mean age of 5·2 years. Three patients were compound-heterozygous for the following mutations: S167fs, Q392X, Y513fs, W648X, V779G. They developed diabetes at a mean age of 6·5 years.
  
  
  CONCLUSIONS
  Mean age of diagnosis of diabetes among the Polish patients was typical for Wolfram syndrome; however, compound-heterozygous patients were slightly older at diabetes onset.
authors.affiliation: Department of Paediatrics, Oncology, Haematology and Diabetology, Medical University of Lodz, Lodz, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Zmyslowska
authors.forename: M
authors.initials: M
authors.lastname: Borowiec
authors.forename: K
authors.initials: K
authors.lastname: Antosik
authors.forename: M
authors.initials: M
authors.lastname: Szalecki
authors.forename: A
authors.initials: A
authors.lastname: Stefanski
authors.forename: B
authors.initials: B
authors.lastname: Iwaniszewska
authors.forename: M
authors.initials: M
authors.lastname: Jedrzejczyk
authors.forename: I
authors.initials: I
authors.lastname: Pietrzak
authors.forename: W
authors.initials: W
authors.lastname: Mlynarski
mesh_terms: D000293:Adolescent; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation / Q000235:genetics*; D011044:Poland; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D044465:White People / Q000235:genetics; D014929:Wolfram Syndrome / Q000235:genetics*; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein