Genetic epidemiology of MODY in the Czech republic: new mutations in the MODY genes HNF-4alpha, GCK and HNF-1alpha
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Diabetes Mellitus, Type 2 genetics MeSH
- Child MeSH
- DNA-Binding Proteins * MeSH
- Adult MeSH
- Phosphoproteins genetics MeSH
- Gene Frequency * MeSH
- Genetic Testing MeSH
- Glucokinase genetics MeSH
- Hepatocyte Nuclear Factor 1-alpha MeSH
- Hepatocyte Nuclear Factor 1-beta MeSH
- Hepatocyte Nuclear Factor 1 MeSH
- Hepatocyte Nuclear Factor 4 MeSH
- Nuclear Proteins * MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Mutation * MeSH
- Child, Preschool MeSH
- Basic Helix-Loop-Helix Leucine Zipper Transcription Factors MeSH
- Transcription Factors genetics MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- DNA-Binding Proteins * MeSH
- Phosphoproteins MeSH
- Glucokinase MeSH
- Hepatocyte Nuclear Factor 1-alpha MeSH
- Hepatocyte Nuclear Factor 1-beta MeSH
- Hepatocyte Nuclear Factor 1 MeSH
- Hepatocyte Nuclear Factor 4 MeSH
- HNF1A protein, human MeSH Browser
- HNF1B protein, human MeSH Browser
- HNF4A protein, human MeSH Browser
- Nuclear Proteins * MeSH
- MLX protein, human MeSH Browser
- Basic Helix-Loop-Helix Leucine Zipper Transcription Factors MeSH
- Transcription Factors MeSH
AIMS/HYPOTHESIS: 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. CONCLUSION/INTERPRETATION: 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.
See more in PubMed
Diabetologia. 1999 Jan;42(1):121-3 PubMed
N Engl J Med. 2001 Sep 27;345(13):971-80 PubMed
Eur J Endocrinol. 2000 Apr;142(4):380-6 PubMed
Diabetologia. 1997 Aug;40(8):980-3 PubMed
Diabetologia. 2001 Jul;44(7):898-905 PubMed
Diabetes. 1997 Oct;46(10):1652-7 PubMed
Diabetes. 2001 Feb;50 Suppl 1:S94-100 PubMed
Diabetologia. 1997 Feb;40(2):217-24 PubMed
Diabetologia. 2001 Jun;44(6):775-8 PubMed
Chronic Mild Hyperglycemia in GCK-MODY Patients Does Not Increase Carotid Intima-Media Thickness
Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents
