[Molecular diagnosis on indication of maturity onset diabetes of the young; results from 184 patients].
OBJECTIVE
To describe the results of mutation analysis of the genes involved in maturity onset diabetes of the young (MODY) types 1-3.


METHODS
Descriptive.


METHODS
In the period July 2000-October 2003 the DNA from 184 possible MODY patients was analysed for the presence of mutations of the genes involved in MODY types 1, 2 and 3. The patients fulfilled at least one of the following criteria: diabetes mellitus had been diagnosed before the age of 25, or at least before the age of 40, there was a family history of diabetes mellitus at an early age, there were no characteristics to indicate diabetes mellitus type 1 or 2.


RESULTS
In the blood of 65 patients (35%) a pathogenic gene mutation was found. A total of 45 patients had a mutation in the HNF-1alpha-gene (which is linked to MODY3), 11 in the glucokinase gene (MODY2) and 9 in the HNF-4alpha-gene (MODY1). Of all the HNF-1alpha-gene mutations, the insertion of a C in codon 291 was the most frequently seen (in 11 families). A mutation in exon 9 of the HNF-1alpha-gene was also shown in 9 apparently non-related families, which probably was a founder mutation.


CONCLUSIONS
The MODY subtype was found in one third of the selected patients. This diagnosis may have implications in the clinical management of the patient.
Losekoot
M
M
Leids Universitair Medisch Centrum, afd. Klinische Genetica, Centrum voor Humane en Klinische Genetica, Wassenaarseweg 72, 2333 AL Leiden. m.losekoot@lumc.nl
Broekman
A J
AJ
Breuning
M H
MH
de Koning
E J P
EJ
Romijn
J A
JA
Maassen
J A
JA
D000328:Adult; D017668:Age of Onset; D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005941:Glucokinase / Q000235:genetics*; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496592:HNF4A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D005941:Glucokinase