The study, led by Sanford Burnham Prebys Medical Discovery Institute scientists, found a mutation that destabilizes proteins involved in children’s growth.

Researchers at Sanford Burnham Prebys Medical Discovery Institute and an international team of collaborators have discovered a new genetic disease that interferes with brain development.

The findings, published April 3 in Human Genetics and Genomics Advances, detail the scientists’ use of a genetic sequencing technique called whole exome sequencing to identify a faulty, mutated gene.

The biochemical consequences of the mutation are an interference with normal cellular function, associated with an unknown congenital disorder of glycosylation (CDG), an umbrella term for nearly 200 disorders with similar proper protein dysfunction.

In the new study, the team began by conducting whole exome sequencing on two siblings suffering from an unfamiliar neurodevelopmental disorder. They found a mutation shared by the two affected siblings but not by three other siblings showing no signs of the disease.

The genetic error, previously unreported, helped the researchers develop a biochemical test used to diagnose patients with CDGs.

Hudson Freeze, PhD/Image courtesy of Sanford Burnham Prebys

“The glycosylation results from these tests reflected patterns we know well from other CDGs,” Hudson Freeze, PhD, the William W Ruch Distinguished Endowed Chair and director of the Sanford Children’s Health Research Center at Sanford Burnham Prebys, said in a press release.

After confirming the error was a new CDG, the scientists then endeavored to understand why it occurred, noting the mutation prevented stability in the oligosaccharyltransferase (OST) complex of proteins, which is necessary for proper protein function.

“Because the OST complex plays a role in every developmental process, that is why we see a range of neurodevelopmental and other developmental issues in CDGs,” Freeze said.

The new disease, now called RPN1-CDG, brings the number of genes associated with OST complex diseases to eight and contributes to a better understanding CDGs, which will help provide definitive diagnoses to more patients suffering from rare diseases.