Functional evidence for SCN8A splice-donor variant c.4419+1 A > G causing loss of function
We report a child with severe developmental and epileptic encephalopathy carrying a rare SCN8A splice‑site variant. Although its pathogenicity was initially unclear, a minigene assay demonstrated aberrant splicing, indicating a loss‑of‑function mechanism. Integrated clinical, genetic and functional evidence classified the variant as pathogenic, underscoring the importance of splicing assays for interpreting rare SCN8A variants.
Authors
- Tomoyuki Akiyama (ORCID: https://orcid.org/0000-0002-4784-9859)
- Sachiko Miyamoto (ORCID: https://orcid.org/0000-0003-2124-4795)
- Toshiki Takenouchi (ORCID: https://orcid.org/0000-0002-7311-4135)
- Hirotomo Saitsu (ORCID: https://orcid.org/0000-0003-0723-0960)
- Takashi Shibata (ORCID: https://orcid.org/0000-0003-4912-279X)
- Takuma Harasaki
Institutions
- Okayama University (JP)
- Hamamatsu University School of Medicine (JP)
- Okayama University Hospital (JP)
Publication Details
- Journal
- Human Genome Variation
- Published
- 2026-06-29
- DOI
- https://doi.org/10.1038/s41439-026-00356-0
- Primary Topic
- Genomics and Rare Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Takeda Science Foundation
- Japan Agency for Medical Research and Development
- Ministry of Health, Labour and Welfare
- Japan Society for the Promotion of Science