Optical genome mapping identifies clinically relevant somatic structural variation in epilepsy-affected brain tissue.

Optical genome mapping detects somatic structural variants in epilepsy-affected brain tissue, revealing a 13.2kb DEPDC5 deletion at approximately 20% VAF in one patient.

• Why it matters: Somatic variants are a significant cause of epilepsy-related cortical malformations, but current detection methods often miss these variants, limiting diagnostic accuracy and understanding of disease mechanisms.
• What they did: Researchers optimized a protocol for optical genome mapping using high-quality DNA from surgically-resected brain tissue and applied it to four epilepsy patients, identifying large and complex structural variants missed by short-read sequencing.
• The result: The study shows OGM can detect somatic structural variants, such as the DEPDC5 deletion mediated by Alu recombination, suggesting it enhances diagnostic capabilities and understanding of genotype-phenotype relationships in neurological disorders.