Genetic epidemiology of MODY in the Czech republic: new mutations in the MODY genes HNF-4alpha, GCK and HNF-1alpha.

Abstract

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.

• Authors: S Pruhova, J Ek, J Lebl, Z Sumnik, F Saudek, M Andel, O Pedersen, T Hansen
• Journal: Diabetologia (Diabetologia) Vol. 46 Issue 2 Pg. 291-5 (Feb 2003) ISSN: 0012-186X [Print] Germany
• PMID: 12627330 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• DNA-Binding Proteins
• HNF1A protein, human
• HNF1B protein, human
• HNF4A protein, human
• Hepatocyte Nuclear Factor 1-alpha
• Hepatocyte Nuclear Factor 4
• MLX protein, human
• Nuclear Proteins
• Phosphoproteins
• Transcription Factors
• Hepatocyte Nuclear Factor 1
• Hepatocyte Nuclear Factor 1-beta
• Glucokinase

Topics

• Adolescent
• Adult
• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• Child
• Child, Preschool
• Czech Republic
• DNA-Binding Proteins
• Diabetes Mellitus, Type 2 (genetics)
• Female
• Gene Frequency
• Genetic Testing
• Glucokinase (genetics)
• Hepatocyte Nuclear Factor 1
• Hepatocyte Nuclear Factor 1-alpha
• Hepatocyte Nuclear Factor 1-beta
• Hepatocyte Nuclear Factor 4
• Humans
• Male
• Middle Aged
• Mutation
• Nuclear Proteins
• Phosphoproteins (genetics)
• Transcription Factors (genetics)