Diagnosis of maturity onset diabetes of the young (MODY) type 2 – Relevance of genetic testing
Maturity Onset Diabetes of the Young (MODY) is a monogenic form of ß-cell dysfunction. Clinical characteristics include autosomal dominant inheritance, age of onset usually before the age of 45 years, lack of ß-cell-autoimmunity and of insulin resistance. MODY is estimated to account for about 5% of diabetes diagnosed before the age of 45 years but is misdiagnosed as Type 1 or Type 2 diabetes in about 80% of cases. One of the most common Types of MODY in Europe is MODY Type 2 which is caused by mutations in the glucokinase gene (GCK). Heterozygous loss-of-function mutations result in mild hyperglycaemia and were as well identified in women with gestational diabetes.
We present a 45-year-old female patient from Germany. She reported of frequently raised fasting blood glucose, HbA1C 6.5%, BMI 21.5, GAD- and IA-2-autoantibody-negative status and was treated with Metformin and Januvia. Her family history showed that her father and her monozygotic twin suffered from diabetes as well. Genetic testing of MODY Type 2 was initiated in our centre.
Sequence analysis of the coding regions of the GCK gene with corresponding exon-intron boundaries and Multiplex Ligation-Dependent Probe Amplification (MLPA) with SALSA P241-D2 probe mix by MRC-Holland for detection of large deletions and duplications.
Sequence analysis indicated the presence of a novel heterozygous deletion of 35 bp which encompasses parts of intron 6 and exon 7 of the GCK gene. Multiplex Ligation-Dependent Probe Amplification showed neither large deletions nor duplications.
These results show that the diagnosis of MODY should be considered in medical diagnostics of diabetes. Genetic testing is relevant for treatment and prognosis in MODY patients. In addition, genetic counselling is important for MODY2 patients and their relatives due to the autosomal dominant inheritance of the disease and with regard to family planning and obstetric management.