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Department of Molecular Cell and Cancer Biology; Li Weibo Institute for Rare Diseases Research

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Amino Acids, Peptides, and Proteins | Cell Biology | Cells | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Genetics and Genomics | Musculoskeletal Diseases | Nervous System Diseases


Facioscapulohumeral muscular dystrophy (FSHD) has been associated with the genetic and epigenetic molecular features of the CpG-rich D4Z4 repeat tandem array at 4q35. Reduced DNA methylation of D4Z4 repeats is considered part of the FSHD mechanism and has been proposed as a reliable marker in the FSHD diagnostic procedure. We considered the assessment of D4Z4 DNA methylation status conducted on distinct cohorts using different methodologies. On the basis of the reported results we conclude that the percentage of DNA methylation detected at D4Z4 does not correlate with the disease status. Overall, data suggest that in the case of FSHD1, D4Z4 hypomethylation is a consequence of the chromatin structure present in the contracted allele, rather than a proxy of its function. Besides, CpG methylation at D4Z4 DNA is reduced in patients presenting diseases unrelated to muscle progressive wasting, like Bosma Arhinia and Microphthalmia syndrome, a developmental disorder, as well as ICF syndrome. Consistent with these observations, the analysis of epigenetic reprogramming at the D4Z4 locus in human embryonic and induced pluripotent stem cells indicate that other mechanisms, independent from the repeat number, are involved in the control of the epigenetic structure at D4Z4.


D4Z4 macrosatellite, DNA methylation, FSHD1, FSHD2, epigenetics

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© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (

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Salsi V, Magdinier F, Tupler R. Does DNA Methylation Matter in FSHD? Genes (Basel). 2020 Feb 28;11(3):E258. doi: 10.3390/genes11030258. PMID: 32121044. Link to article on publisher's site

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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.