Recent research led by UTHealth Houston scientists has uncovered two genes associated with variants linked to epilepsy, which showed specific traits that make them promising diagnostic biomarkers.

The study is published in Nature Communications.

Led by Dennis Lal, Ph.D., director of the Center for Neurogenetics and associate professor of neurology at McGovern Medical School at UTHealth Houston, the research team analysed data from 1,386 human brain tissues for somatic variants in the genes of individuals undergoing epilepsy surgery. Somatic variants are DNA changes that occur after conception and can only be identified in the brain tissue.

According to the Centers for Disease Control and Prevention (CDC), epilepsy affects approximately 3.4 million people in the United States, and 1 in 3 patients struggle with drug-resistant forms of the condition. By linking epilepsy to specific genetic mutations, the research offers a new framework for understanding the disorder and developing therapies that address its root causes.

The most extensive study of its kind, the research identified two novel genes, DYRK1A and EGFR, and their genetic mutations linked to epileptic brain lesions.

"Discovering these genes not only helps us better understand the biology behind epilepsy but also reveals specific traits in tissues, making them valuable tools for diagnosing the condition," Lal said.

Through the research, Lal and his team confirmed four well-established gene-disease associations and provided evidence for eight more. Once brain tissue testing after surgery becomes clinically available outside of research, these findings could offer long-awaited answers about what causes the condition of these patients with a drug-resistant form of the disease, he said.

The project also revealed that many genes identified with associated variants interact with biological pathways targeted by FDA-approved cancer drugs. While epileptic lesions share genetic similarities with tumours, they differ in several key ways. Neurons—the affected cells in epilepsy—do not replicate like cancer cells, opening opportunities to repurpose existing cancer drugs for epilepsy treatment.

"For those with epilepsy, their caregivers, and health care providers, our research represents a step closer to understanding epilepsy at its most fundamental level while improving patients' quality of life," Lal said.

Co-authors include Christian Bosselman, MD, of Universitätsklinikum Tübingen; Costin Leu, PhD, and Tobias Brünger, PhD, of UTHealth Houston; Lucas Hoffman, MD, Ph.D., of the University of Washington; Katja Kobow Ph.D., of Universitätsklinikum Erlangen; Imad Najm MD, of the Cleveland Clinic; and Ingmar Blumcke, MD, of Universitätsklinikum Erlangen—Institute of Neuropathology.

More information: Christian M. Boßelmann et al, Analysis of 1386 epileptogenic brain lesions reveals association with DYRK1A and EGFR, Nature Communications (2024). DOI: 10.1038/s41467-024-54911-w