Journal article
Smchd1 haploinsufficiency exacerbates the phenotype of a transgenic FSHD1 mouse model
JC de Greef, YD Krom, B den Hamer, L Snider, Y Hiramuki, RFP van den Akker, K Breslin, M Pakusch, DCF Salvatori, B Slütter, R Tawil, ME Blewitt, SJ Tapscott, SM van der Maarel
Human Molecular Genetics | OXFORD UNIV PRESS | Published : 2018
DOI: 10.1093/hmg/ddx437
Abstract
In humans, a copy of the DUX4 retrogene is located in each unit of the D4Z4 macrosatellite repeat that normally comprises 8-100 units. The D4Z4 repeat has heterochromatic features and does not express DUX4 in somatic cells. Individuals with facioscapulohumeral muscular dystrophy (FSHD) have a partial failure of somatic DUX4 repression resulting in the presence of DUX4 protein in sporadic muscle nuclei. Somatic DUX4 derepression is caused by contraction of the D4Z4 repeat to 1-10 units (FSHD1) or by heterozygous mutations in genes responsible for maintaining the D4Z4 chromatin structure in a repressive state (FSHD2). One of the FSHD2 genes is the structural maintenance of chromosomes hinge do..
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Awarded by National Institutes of Health
Funding Acknowledgements
National Institutes of Health (NINDS: PO1 NS069539; NIAMS: RO1 AR066248), the Prinses Beatrix Spierfonds (W.OR14-24), and the Australian National Health and Medical Research Council (GNT1098290). FSH Society and FSHD Canada Foundation research fellowship (FSHS-22015-02) to YH. Bellberry-Viertel Senior Medical Research fellowship to MEB. Work performed at WEHI was also supported by Victorian State Government Operational Infrastructure Support, an NHMRC IRIISS grant (9000220).