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Reduced histone H3K4 trimethylation in oral mucosa of patients with DYT-KMT2B.
- Source :
-
Parkinsonism & related disorders [Parkinsonism Relat Disord] 2024 Jul; Vol. 124, pp. 107018. Date of Electronic Publication: 2024 May 27. - Publication Year :
- 2024
-
Abstract
- 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.<br />Objectives: To explore the altered H3K4me3 levels in non-neural tissue of DYT-KMT2B patients.<br />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.<br />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.<br />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.<br />Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Naomichi Matsumoto reports financial support was provided by Takeda Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Subjects :
- Adolescent
Adult
Child
Female
Humans
Male
Middle Aged
Young Adult
Fibroblasts metabolism
Keratinocytes metabolism
Methylation
Dystonic Disorders genetics
Dystonic Disorders metabolism
Histone-Lysine N-Methyltransferase genetics
Histone-Lysine N-Methyltransferase metabolism
Histones metabolism
Histones genetics
Mouth Mucosa metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-5126
- Volume :
- 124
- Database :
- MEDLINE
- Journal :
- Parkinsonism & related disorders
- Publication Type :
- Academic Journal
- Accession number :
- 38810319
- Full Text :
- https://doi.org/10.1016/j.parkreldis.2024.107018