Scientists have discovered the cause of a rare condition within a part of the genome that has been largely unexplored in medical genetics. A team at the University of Exeter has found genetic changes in a region that controls the activity of the genome, turning on or off genes, and in doing so they have found a key that could unlock other causes of rare conditions.
The finding, published in Nature Genetics, is a very rare case of a cause of disease that only results from changes outside the exome, the region of the genome that codes for genes. It is also found that changes have been shown to affect a gene – known as HK1 – that does not normally have a role in the relevant body tissue – in this case, the pancreas.
The team sequenced the genomes of 17 individuals with Congenital Hyperinsulinism with an unexplained cause, revealing a revelation - the genetic variants that were causing the disease did not occur within a protein but within a ‘regulatory switch’ which is important for turning on and off a protein in the pancreas.
The impact of the genetic variants was that HK1 was turned on in the pancreases of patients with Congenital Hyperinsulinism. The gene, which leads to insulin being produced even when blood sugar levels are low, is usually turned off in the pancreas. But the team found it was active – meaning it was working to lower blood sugar to dangerous levels. Studying a unique collection of pancreatic tissue confirmed this hypothesis.
