Optical genome mapping identifies clinically relevant somatic structural variation in epilepsy-affected brain tissue
at approximately 20% VAF - consistent with the established two-hit model in DEPDC5-associated lesional epilepsies. By resolving the breakpoints in PacBio HiFi sequencing data, we identify a mechanism for this somatic deletion, mediated by recombination of two Alu elements flanking the region. Our findings demonstrate that OGM is a robust and complementary tool for detecting somatic structural variation in human brain tissue, with potential to improve diagnostic yield and refine genotype-phenotype correlations in neurological disorders.
Authors
- Maria Elena Hernandez Gonzalez
- Jonathan Pindrik (ORCID: https://orcid.org/0000-0002-8520-8825)
- Lakshmi P. Rao Venkata (ORCID: https://orcid.org/0009-0006-0110-6845)
- Diana Thomas (ORCID: https://orcid.org/0000-0001-7004-2036)
- Daniel R. Boué (ORCID: https://orcid.org/0000-0003-2262-5274)
- Ammar Shaikhouni (ORCID: https://orcid.org/0000-0002-3527-4920)
- Elaine R. Mardis (ORCID: https://orcid.org/0000-0002-5892-1553)
- Eileen Stonerock
- J. Leonard
- Adam P. Ostendorf (ORCID: https://orcid.org/0000-0002-9994-6650)
- Anthony R. Miller (ORCID: https://orcid.org/0000-0001-5012-9222)
- Christopher R. Pierson (ORCID: https://orcid.org/0000-0002-5553-3096)
- James J. Anderson (ORCID: https://orcid.org/0009-0004-7326-5787)
- Allison Daley
- Tracy A Bedrosian
- Lauren Mashburn-Warren
- Daniel C Koboldt
- Katherine E Miller
Institutions
- Nationwide Children's Hospital (US)
- The Ohio State University (US)
Publication Details
- Journal
- medRxiv
- Published
- 2026-04-27
- DOI
- https://doi.org/10.64898/2026.04.18.26350985
- Primary Topic
- Genomics and Rare Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00