Rare genetic mutations known as “loss-of-function” mutations, because they lead to severe disruption in a gene’s functioning, are thought to play an important role in causing schizophrenia. In a new study led by 2010 NARSAD Distinguished Investigator Grantee Maria Karayiorgou, M.D., and her colleague, two-time NARSAD Young Investigator Grantee Joseph Gogos, M.D., Ph.D., of Columbia University Medical Center, researchers have identified new mutations in the SETD1A gene that they believe are linked to the development of this mental illness.

The researchers used high-throughput DNA sequencing technology to scan the protein-coding part of the genome, called the exome, of 231 people with schizophrenia and their parents to examine the role of loss-of-function genetic mutations—both “de novo” mutations that arise spontaneously and are not present in either parent and inherited mutations that are passed on from parent to child. Their findings, published May 21st in Neuron, show that two de novo loss-of-function mutations in SETD1A were found in two different people with schizophrenia—a convergence almost unheard of for rare variants.

Dr. Karayiorgou told Medical News Today that the findings help "define a specific genetic mechanism" that in part explains the development of schizophrenia.

The SETD1A gene plays a role in what is called chromatin modification—an important cellular process that helps regulate gene expression. Problems with this process of chromatin modification can lead to the incorrect expression of many different genes, creating faulty wiring in the brain during development, when gene expression is particularly intense. It could also disturb how the environment impinges upon gene expression, both early and later in life.

The team's findings may lead to new strategies for early detection and treatment of schizophrenia according to Dr. Gogos. "A clinical implication of this finding is the possibility of using the number and severity of mutations involved in chromatin regulation as a way to identify children at risk of developing schizophrenia and other neurodevelopmental disorders,” he told Medical News Today.

Since manifestation of the symptoms of schizophrenia occurs most often between the ages of 16 and 30, identifying these mutations in childhood could lead to important early intervention techniques to restore proper gene expression before the illness fully manifests.

Read more about this study from the Schizophrenia Research Forum.

Read the abstract for this research.

Read an article in Medical News Today.