<scp> <i>TBK</i> </scp> <i>1</i> ‐Associated Primary Lateral Sclerosis Followed by Right Temporal Variant Frontotemporal Dementia
We report a 58-year-old woman with a novel splice-site variant in the TANK-binding kinase 1 (TBK1:c.993-2A>C p.Ala332TyrfsTer39) who sequentially developed primary lateral sclerosis (PLS) followed by right temporal variant frontotemporal dementia (rtvFTD). Neuroimaging demonstrated right anterior temporal atrophy before cognitive symptoms, and prosopagnosia represented the earliest manifestation of rtvFTD. Molecular analysis revealed reduced levels of correctly spliced TBK1 transcripts, consistent with haploinsufficiency. Given the shared involvement of TDP-43 pathology in both PLS and rtvFTD, this case indicates TBK1 dysfunction as a fundamental genetic factor underlying the coexistence of these phenotypes, underscoring the clinical value of early neuroimaging and genetic evaluation.
Authors
- Tomoyasu Matsubara (ORCID: https://orcid.org/0000-0002-7559-8284)
- Eriko Koshimizu (ORCID: https://orcid.org/0000-0001-9947-3315)
- Yoichi Otomi (ORCID: https://orcid.org/0000-0002-8960-3662)
- Ryosuke Miyamoto (ORCID: https://orcid.org/0000-0001-6434-9541)
- Kazuya Tachibana (ORCID: https://orcid.org/0000-0003-2520-8142)
- Yuki Kuwano
- Mizuki Morimoto
- N. Kihara
- Yusuke Osaki
- Koji Fujita
- Hiroki Yamazaki
- Yuishin Izumi
- Satoko Miyatake
- Nazere Keyoumu
- Masafumi Harada
- Kenji Ishibashi
- Hiroyuki Morino
- Naomichi Matsumoto
- Suzuran Saito
Institutions
- Hiroshima University (JP)
- Shiga University of Medical Science (JP)
- Shiga University (JP)
- Yokohama City University Hospital (JP)
- National Center of Neurology and Psychiatry (JP)
- Tokushima University Hospital (JP)
- Tokyo Metropolitan Institute of Gerontology (JP)
- Kagawa Prefectural Central Hospital (JP)
- Yokohama City University (JP)
- Tokushima University (JP)
Publication Details
- Journal
- Annals of Clinical and Translational Neurology
- Published
- 2026-02-05
- DOI
- https://doi.org/10.1002/acn3.70329
- Primary Topic
- Amyotrophic Lateral Sclerosis Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Japan Agency for Medical Research and Development
- Ministry of Health, Labour and Welfare
- Japan Society for the Promotion of Science