{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:06:36Z","timestamp":1790517996068,"version":"4.1.0"},"reference-count":115,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T00:00:00Z","timestamp":1582848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GUP13012"],"award-info":[{"award-number":["GUP13012"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007393","name":"Association Fran\u00e7aise contre les Myopathies","doi-asserted-by":"publisher","award":["TRIM-RD"],"award-info":[{"award-number":["TRIM-RD"]}],"id":[{"id":"10.13039\/100007393","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009879","name":"Regione Emilia-Romagna","doi-asserted-by":"publisher","award":["RARER"],"award-info":[{"award-number":["RARER"]}],"id":[{"id":"10.13039\/501100009879","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/genes11030258","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T07:35:30Z","timestamp":1583134530000},"page":"258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Does DNA Methylation Matter in FSHD?"],"prefix":"10.3390","volume":"11","author":[{"given":"Valentina","family":"Salsi","sequence":"first","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 4, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0159-9559","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9rique","family":"Magdinier","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, INSERM, MMG, U 1251, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3797-1789","authenticated-orcid":false,"given":"Rossella","family":"Tupler","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 4, 41121 Modena, Italy"},{"name":"Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, 4, 41121 Modena, Italy"},{"name":"Department of Molecular Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01003, USA"},{"name":"Li Weibo Institute for Rare Diseases Research at the University of Massachusetts Medical School, Worcester, MA 01003, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1212\/WNL.0000000000000797","article-title":"EPopulation-based incidence and prevalence of facioscapulohumeral dystrophy","volume":"83","author":"Deenen","year":"2014","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1111\/j.1399-0004.2009.01158.x","article-title":"Facioscapulohumeral muscular dystrophy: Epidemiological and molecular study in a north-east Italian population sample","volume":"75","author":"Mostacciuolo","year":"2009","journal-title":"Clin. 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