A team led by researchers at Western University have identified a previously unidentified genetic mutation that leads to intellectual disability and autism spectrum disorder, providing answers to a group of patients with a previously undiagnosed syndrome.

While patients with neurodevelopmental disorders like intellectual disability and autism spectrum disorder have clinical features which overlap, there is an enormous diversity of underlying genetic causes. This presents a challenge for making specific diagnosis for many patients.

The study published in the journal PLoS Genetics and led by Jamie Kramer, PhD, assistant professor at Western’s Schulich School of Medicine & Dentistry uncovers a new syndrome characterized by a mutation in a gene called KMT2C.

“It started with patients that were suspected to have Kleefstra syndrome, but didn’t have the genetic mutation for it,” said Kramer who is also a Canada Research Chair in Neuroepigentics. “Kleefstra syndrome is characterized by mutations in EHMT1, and although these patients had similar clinical symptoms to Kleefstra syndrome, they didn’t have the mutation.”

Kramer and his team honed in on KMT2C and have so far shown the mutation in a cohort of six patients with intellectual disability and autism spectrum disorder. Kramer says now that the mutation is known, there will likely be more patients diagnosed with this new syndrome and he hopes this will give some comfort to those families and may help to inform treatment options in the future.

Using fruit flies, the team is trying to understand the basic biological mechanisms underlying these disorders. They demonstrated that mutations in the fly version of KMT2C caused memory deficits, and resulted in changes in gene activity in the brain.

“We found that was very similar to what you find when you knock out the Kleefstra syndrome gene in flies,” said Kramer. By identifying and understanding the common processes that are disrupted in autism spectrum disorder and intellectual disability in all of the different gene mutations, Kramer says researchers can then start to think about therapies that target those common processes.