Non-coding cis-regulatory variants in HK1 cause congenital hyperinsulinism with variable disease severity.

ABSTRACT:

Background

We recently reported non-coding variants in a cis-regulatory element of the beta-cell disallowed gene hexokinase 1 (HK1) as a novel cause of congenital hyperinsulinism. These variants lead to a loss of repression of HK1 in pancreatic beta-cells, causing insulin secretion during hypoglycaemia. In this study, we aimed to determine the prevalence, genetics, and phenotype of HK1-hyperinsulinism by screening a large international cohort of patients living with the condition.

Methods

We screened the HK1 cis-regulatory region in 1761 probands with hyperinsulinism of unknown aetiology who had been referred to one of three large European genomics laboratories.

Results

We identified a HK1 variant in 89/1761 probands (5%) and 63 family members. Within the Exeter HI co

SUBMITTER: Bennett JJ 

PROVIDER: S-EPMC11874398 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature