title: Genetic epidemiology of MODY in the Czech republic: new mutations in the MODY genes HNF-4alpha, GCK and HNF-1alpha.
abstract: OBJECTIVE
  The aim of this study was to examine the prevalence and nature of mutations in HNF4alpha/MODY1, GCK/MODY2 and HNF-1alpha/MODY3 genes in Czech subjects with clinical diagnosis of MODY.
  
  
  METHODS
  We studied 61 unrelated index probands of Czech origin (28 males, 33 females) with a clinical diagnosis of MODY and 202 family members. The mean age of probands was 22.7+/-12.0 years (range, 6-62) and the mean age at the first recognition of hyperglycaemia was 14.7+/-6.0 years (range, 1-25). The promotor and coding regions inclusive intron exon boundaries of the HNF-4alpha, GCK and HNF-1alpha genes were examined by PCR-dHPLC (HNF-1alpha and GCK) and direct sequencing.
  
  
  RESULTS
  We identified 20 different mutations in the HNF-4alpha, GCK and HNF-1alpha in 29 families (48% of all families studied), giving a relative prevalence of 5% of MODY1, 31% of MODY2 and 11.5% of MODY3 among the Czech kindred with MODY. Three of 3, 10 of 11 and 1 of 6 of the mutations identified in HNF-4alpha, GCK and HNF-1alpha respectively, were new.
  
  
  CONCLUSIONS
  Of the families 48% carried mutations in the MODY1-3 genes and of the identified mutations 70% were new. In 52% of Czech families with clinical characteristics of MODY, no mutations were found in the analysed genes. This finding shows that the majority of MODY mutations in a central European population are local and that other MODY genes could be responsible for autosomal dominant transmission of diabetes mellitus.
authors.affiliation: Department of Paediatrics, 3rd Faculty of Medicine, Charles University, Vinohradska 159, 100-81 Prague 10, Czech Republic.
authors.forename: S
authors.initials: S
authors.lastname: Pruhova
authors.forename: J
authors.initials: J
authors.lastname: Ek
authors.forename: J
authors.initials: J
authors.lastname: Lebl
authors.forename: Z
authors.initials: Z
authors.lastname: Sumnik
authors.forename: F
authors.initials: F
authors.lastname: Saudek
authors.forename: M
authors.initials: M
authors.lastname: Andel
authors.forename: O
authors.initials: O
authors.lastname: Pedersen
authors.forename: T
authors.initials: T
authors.lastname: Hansen
mesh_terms: D000293:Adolescent; D000328:Adult; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002648:Child; D002675:Child, Preschool; D018153:Czech Republic; D004268:DNA-Binding Proteins; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D005941:Glucokinase / Q000235:genetics*; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; C496592:HNF4A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; C403128:MLX protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D005941:Glucokinase