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アカガワ ヒロユキ
AKAGAWA Hiroyuki
赤川 浩之 所属 研究施設 研究施設 職種 准教授 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Reduced histone H3K4 trimethylation in oral mucosa of patients with DYT-KMT2B. |
| 掲載誌名 | 正式名：Parkinsonism & related disorders 略 称：Parkinsonism Relat Disord ISSNコード：18735126/13538020 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 124,pp.107018 |
| 著者・共著者 | Naoto Sugeno, Satoko Kumada, Hirofumi Kashii, Jun Ikezawa, Toshitaka Kawarai, Takaaki Nakamura, Ako Miyata, Shun Ishiyama, Kazuki Sato, Shun Yoshida, Hutoshi Sekiguchi, Kohei Hamanaka, Satoko Miyatake, Noriko Miyake, Naomichi Matsumoto, Hiroyuki Akagawa, Kenjiro Kosaki, Hiroshi Yoshihashi, Takafumi Hasegawa, Masashi Aoki |
| 発行年月 | 2024/07 |
| 概要 | BACKGROUND:DYT-KMT2B, also known as DYT28, is a childhood-onset hereditary dystonia caused by KMT2B mutation. The pathogenesis of DYT-KMT2B involves haploinsufficiency of KMT2B, an enzyme that catalyzes specific histone methylation (H3K4me3). Dysmorphic features in patients with DYT-KMT2B suggest that KMT2B dysfunction may extend beyond the neuronal system. Therefore, valuable diagnostic insights may be obtained from readily available tissue samples.OBJECTIVES:To explore the altered H3K4me3 levels in non-neural tissue of DYT-KMT2B patients.METHODS:A database analysis was performed to determine in which parts of the body and in which cells KMT2B is highly expressed. Twelve clinically and genetically diagnosed patients with DYT-KMT2B and 12 control subjects participated in this study. Oral mucosa-derived purified histone proteins were analyzed using Western blotting with anti-H3K4me3 and anti-H4 antibodies.RESULTS:Higher expression of KMT2B was observed in oral keratinocytes and gingival fibroblasts, constituting the oral mucosa. In oral mucosa analyses, DYT-KMT2B cases exhibited markedly reduced H3K4me3 levels compared with the controls. Using a cutoff window of 0.90-0.98, the H3K4me3/H4 expression ratio was able to distinguish patient groups.CONCLUSIONS:Oral mucosa H3K4me3 analysis is currently not sufficient as a diagnostic tool for DYT-KMT2B, but has the advantage for screening test since it is a non-invasive means. |
| DOI | 10.1016/j.parkreldis.2024.107018 |
| PMID | 38810319 |