Two Japanese families with adult-onset leukoencephalopathy caused by pathogenic variants in CST3
CST3 (NM_000099.4) encodes cystatin C, whose C-terminal truncating variants in this gene have recently been reported to cause adult-onset leukoencephalopathy, characterized by headaches, transient neurological symptoms, and distinct imaging findings. We present four patients from two Japanese families, including one with a novel variant (c.358-2_395del). Three patients from one family developed chronic headaches around the age of 20, whereas the patient from the other family remained asymptomatic until his fifties. mRNA analysis of the patient with c.358-2_395del revealed a splicing alteration leading to an in-frame deletion (p.Lys120_Gln133del), representing the first CST3 variant that does not result in a truncated protein. These findings broaden our understanding of the clinical and genetic spectra of CST3-related leukoencephalopathy (114 words).
Authors
- Hiroyuki Ishiura (ORCID: https://orcid.org/0000-0003-2975-7309)
- Ryo Kurokawa (ORCID: https://orcid.org/0000-0002-1186-8900)
- Yosuke Kawai
- Kazutaka Shiomi
- Junko Nomoto
- Akihiko Mitsutake (ORCID: https://orcid.org/0000-0002-9165-0193)
- Ryoji Goto (ORCID: https://orcid.org/0000-0002-1693-9915)
- Katsushi Tokunaga (ORCID: https://orcid.org/0000-0001-5501-0503)
- Jun Mitsui (ORCID: https://orcid.org/0000-0001-7425-4765)
- Nozomu Matsuda (ORCID: https://orcid.org/0000-0003-3773-6778)
- Shoji Tsuji (ORCID: https://orcid.org/0000-0001-5602-5686)
- Masaki Tanaka (ORCID: https://orcid.org/0000-0002-6177-1314)
- Kenta Orimo (ORCID: https://orcid.org/0000-0003-3649-5570)
- Yosuke Omae (ORCID: https://orcid.org/0000-0001-9978-4869)
- Takashi Matsukawa (ORCID: https://orcid.org/0000-0002-5925-9450)
- Kazuaki Kanai (ORCID: https://orcid.org/0000-0002-2174-002X)
- Tatsushi Toda
- Yumiko Kuromi
Institutions
- University of Miyazaki (JP)
- Fukushima Medical University (JP)
- Okayama University (JP)
- National Center for Global Health and Medicine (JP)
- University of Miyazaki Hospital (JP)
- The University of Tokyo (JP)
- International University of Health and Welfare (JP)
Publication Details
- Journal
- Journal of the Neurological Sciences
- Published
- 2025-09-27
- DOI
- https://doi.org/10.1016/j.jns.2025.123708
- Citations
- 1
- Primary Topic
- RNA regulation and disease
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Japan Agency for Medical Research and Development
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science