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Mechanisms of pathogenesis of missense mutations on the KDM6A-H3 interaction in type 2 Kabuki Syndrome

Authors :
Francesco Petrizzelli
Tommaso Biagini
Alessandro Barbieri
Luca Parca
Noemi Panzironi
Stefano Castellana
Viviana Caputo
Angelo Luigi Vescovi
Massimo Carella
Tommaso Mazza
Source :
Computational and Structural Biotechnology Journal, Vol 18, Iss , Pp 2033-2042 (2020)
Publication Year :
2020
Publisher :
Elsevier, 2020.

Abstract

Mutations in genes encoding for histone methylation proteins are associated with several developmental disorders. Among them, KDM6A is the disease causative gene of type 2 Kabuki Syndrome, a rare multisystem disease. While nonsense mutations and short insertions/deletions are known to trigger pathogenic mechanisms, the functional effects of missense mutations are still uncharacterized. In this study, we demonstrate that a selected set of missense mutations significantly hamper the interaction between KDM6A and the histone H3, by modifying the dynamics of the linker domain, and then causing a loss of function effect.

Details

Language :
English
ISSN :
20010370
Volume :
18
Issue :
2033-2042
Database :
Directory of Open Access Journals
Journal :
Computational and Structural Biotechnology Journal
Publication Type :
Academic Journal
Accession number :
edsdoj.5f371d571e554adabd228f2298c8b58a
Document Type :
article
Full Text :
https://doi.org/10.1016/j.csbj.2020.07.013