Reduced histone H3K4 trimethylation in oral mucosa of patients with DYT-KMT2B

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. To explore the altered H3K4me3 levels in non-neural tissue of DYT-KMT2B patients. 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. 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. 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. •DYT-KMT2B is a disease characterized by dystonia, but also has systemic features.•KMT2B is an enzyme that catalyzes H3K4me3 and is expressed in oral epithelium cells.•H3K4me3 was decreased in oral mucosa derived from DYT-KMT2B patients.•Oral mucosa H3K4me3 analysis may be an adjunctive diagnostic tool for DYT-KMT2B cases.