Reduced histone H3K4 trimethylation in oral mucosa of patients with DYT-KMT2B.
Parkinsonism Relat Disord
; 124: 107018, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38810319
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.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.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Histones
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Histone-Lysine N-Methyltransferase
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Dystonic Disorders
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Mouth Mucosa
Limits:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
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Middle aged
Language:
En
Year:
2024
Type:
Article