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Curr Opin Genet Dev. 2015 Aug;33:56-61. doi: 10.1016/j.gde.2015.08.007. Epub 2015 Sep 7.

Genetic and epigenetic contributors to FSHD.

Author information

1
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
2
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
3
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: maarel@lumc.nl.

Abstract

Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant muscle disorder characterized by distinct chromatin changes including DNA hypomethylation of the D4Z4 macrosatellite repeat array on a disease-permissive 4qA allele and aberrant expression of the D4Z4-embedded DUX4 retrogene in skeletal muscle. Insufficient epigenetic repression of the D4Z4 repeat is the result of at least two different genetic mechanisms leading to two forms of disease, FSHD1 and FSHD2. In the case of FSHD1, a contraction of the D4Z4 repeat array is disease causing whereas FSHD2 is most often caused by mutations in the structural maintenance of chromosomes hinge domain 1 (SMCHD1) gene. Recent studies indicate that a combination of genetic and epigenetic factors that act on the D4Z4 repeat array determine the probability of DUX4 expression in skeletal muscle and disease penetrance and progression.

PMID:
26356006
PMCID:
PMC4674299
DOI:
10.1016/j.gde.2015.08.007
[Indexed for MEDLINE]
Free PMC Article

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