Patient recruitment strategy for family studies investigating novel genetic causes of maturity-onset diabetes of the young

Abstract

Abstract

A small but significant minority of patients with diabetes have a defect in a single gene that is responsible for their diabetes. Determining the genetic subtype of their diabetes not only offers insights into the pathophysiology of diabetes, but also helps clinicians to determine the most appropriate treatment.

Maturity-onset diabetes of the young (MODY) is an autosomal dominant subtype of diabetes. Mutations in the glucokinase (GCK) gene result in mildly elevated fasting hyperglycaemia (>5.5mmol/L) throughout life. Our aim was to recruit families with this phenotype who do not have a GCK gene mutation in order to identify a novel genetic cause for their diabetes.

The UK MODY database, which details all subjects who have undergone a genetic test for MODY, was used as a resource to identify patients with a phenotype suggestive of GCK-MODY in whom no GCK mutation had been found. Interested families were visited in their homes and blood was taken for biochemical analysis and DNA extraction. Anthropometric measurements were recorded on all recruited family members.

Twelve probands were identified but two were excluded as their phenotype was no longer consistent with GCK-MODY. Four were already consented for research and the remaining six were contacted through the MODY link nurses. To date, six multi-generation families have been collected.

Our novel recruitment strategy, involving the UK MODY database in combination with a research nurse and a nationwide team of MODY link nurses, has proved successful in identifying a small subset of families who are a resource for genetic studies. Our unique approach provides a recruitment protocol that can be adapted for other genetic studies.