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

DEPDC5

Somatic structural variant detection by optical genome mapping in resected brain tissue; 13.2 kb somatic deletion of DEPDC5 mediated by recombination of two Alu elements (two-hit model).

The authors optimise an optical genome mapping (OGM) protocol for surgically resected brain tissue, reaching about 450x effective coverage suitable for low-allele-fraction somatic variants. Applied to four patients with epilepsy, OGM identifies large and complex structural variants, most of which are not captured by short-read exome sequencing of the same specimen. In a patient with a known germline DEPDC5 variant, it reveals a somatic 13.2 kb deletion at about 20% VAF, consistent with the two-hit model. PacBio HiFi sequencing resolves the breakpoints and shows recombination between two Alu elements.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The value is in showing that short-read exome sequencing of brain tissue misses somatic structural variants, even in a known gene such as DEPDC5. With four patients the demonstration remains exploratory: the gain in diagnostic yield and routine feasibility are not quantified. Access to surgical tissue also restricts use to a narrow population.

Analysis by Dr Thibaut Benquey