Understanding how genetics, environment and interventions influence the nature and severity of intellectual disability.

Summary

Changes in genes that provide instructions for a potassium (KATP) channel in our pancreas and brain can lead to reduced or increased insulin levels. This causes neonatal diabetes(NDM), with raised blood glucose, or congenital hyperinsulinism(CHI), with low blood glucose. Knowing the genetic change in each individual allows specific treatments that improve glucose control. Many affected individuals also have problems with brain development, including intellectual disability (ID). This can be due to the faulty channel in the brain, and may also respond to specific treatment(s). However, environmental factors like very low blood glucose also play a role. This research will find out more about how genetic and environmental factors impact ID in people with KATP-channel-related conditions.

How are we doing it?

I will study people living with KATP-channel-related conditions. I will collect clinical information from their medical records and do face-to-face interviews with some individuals. I will investigate the effects of the following on nature and severity of ID and other problems:
1. Genetics: the impact of different changes in KATP-channel genes
2. Interventions: the impact of different treatments
3. Environment: the impact of very low blood sugar

I will continue to involve patient groups in study development and dissemination of results. I will identify ways to better engage and include people with ID in these discussions.

What happens next?

I will work with patients and collaborators to undertake this research, which will provide insights into the role(s) of brain KATP channels and how genetic variants, interventions and hypoglycaemia influence ID variability in NDM and CHI. This will have clinical impact by informing prognostics and treatment in these conditions, in-keeping with the BRC diabetes theme. Importantly, the research will represent an exemplar for exploring variability and targeted treatment in other forms of genetic ID. This will inform future funding applications.

Funding

NIHR Exeter BRC.

People Involved

Professor Andrew Hattersley, Professor Sarah Flanagan, Professor Maggie Shepherd, Associate Professor Elisa De Franco.