Moleculaire diagnostiek bij aanwijzingen voor 'maturity onset diabetes of the young'; resultaten bij 184 patiënten

To describe the results of mutation analysis of the genes involved in maturity onset diabetes of the young (MODY) types 1-3.

Design

Descriptive.

Method

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-1α-gene (which is linked to MODY3), 11 in the glucokinase gene (MODY2) and 9 in the HNF-4α-gene (MODY1). Of all the HNF-1α-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-1α-gene was also shown in 9 apparently non-related families, which probably was a founder mutation.

Conclusion

The MODY subtype was found in one third of the selected patients. This diagnosis may have implications in the clinical management of the patient.

Ned Tijdschr Geneeskd 2005;149:139-43