Detecting Rare Genetic Mutations Linked to Hyperinsulinism in Pancreatic Tissue

Detection of hyperinsulinism-causing low-level mosaic variants in the regulatory region of HK1 in formalin-fixed, paraffin embedded pancreatic tissue using laser-capture microdissection

Summary

Using laser-capture microdissection, we aim to dissect out a subset of islets that aberrantly express hexokinase1, and sequence the DNA extracted from these islets to provide a genetic diagnosis for congenital hyperinsulinism.

How are we doing it?

I will identify the islets that express HK1, and therefore are likely to harbour a variant within the previously identified critical regulatory region of the HK1 gene. These islets will be laser-dissected from the tissue and the DNA from these islets will be sequenced.

What happens next?

This technique may be applied to other situations where a low-level mosaic variant is suspected to cause hyperinsulinism or other rare disease.

Funding

NIHR Exeter BRC.

People Involved

Jasmin Bennett, Sarah Flanagan.