Objective: To explore the altered H3K4me3 levels in non-neural tissue of DYT-KMT2B patients.

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.

Method: 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. We further analyzed the significance of H3K4me3 in patients with DYT-KMT2B using publicity available datasets.

Results: DYT-KMT2B cases exhibited markedly reduced H3K4me3 levels compared with the controls, inversely correlating with disease duration. Additionally, a reanalysis of publicly available datasets concerning DNA methylation also demonstrated that KMT2B remained inactive in DYT-KMT2B.

Conclusion: Oral mucosa H3K4me3 analysis is a noninvasive and useful adjunctive diagnostic tool for DYT-KMT2B cases.

References: Sugeno N, Hasegawa T, Haginoya K, et al. Detection of Modified Histones from Oral Mucosa of a Patient with DYT-KMT2B Dystonia. Mol Syndromol 2023;14(6):461-468.

« Back to 2024 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/exploring-the-non-invasive-epigenetic-screening-test-for-hereditary-dystonia-dyt-kmt2b/