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These two genotypes share a phenotype characterized by progressive and often asymmetric muscle weakening and atrophy, and common epigenetic alterations of the D4Z4 repeat. All together, these epigenetic changes converge the two genetic forms into one disease and explain the derepression of the\n                    <jats:italic>DUX4<\/jats:italic>\n                    gene, which is otherwise kept epigenetically silent in skeletal muscle.\n                    <jats:italic>DUX4<\/jats:italic>\n                    is consistently transcriptionally upregulated in FSHD1 and FSHD2 skeletal muscle cells where it is believed to exercise a toxic effect. Here we provide a review of the recent literature describing the progress in understanding the complex genetic and epigenetic architecture of FSHD, with a focus on one of the consequences that these epigenetic changes inflict, the DUX4\u2010induced immune deregulation cascade. Moreover, we review the latest therapeutic strategies, with particular attention to the potential of epigenetic correction of the FSHD locus.\n                  <\/jats:p>","DOI":"10.1111\/cge.13726","type":"journal-article","created":{"date-parts":[[2020,2,22]],"date-time":"2020-02-22T00:49:52Z","timestamp":1582332592000},"page":"799-814","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Consequences of epigenetic derepression in facioscapulohumeral muscular dystrophy"],"prefix":"10.1111","volume":"97","author":[{"given":"Anna","family":"Greco","sequence":"first","affiliation":[{"name":"Department of Neurology, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center  Nijmegen The Netherlands"},{"name":"Department of Experimental Internal Medicine Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8829-4378","authenticated-orcid":false,"given":"Remko","family":"Goossens","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9867-9047","authenticated-orcid":false,"given":"Baziel","family":"van Engelen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8103-711X","authenticated-orcid":false,"given":"Silv\u00e8re M.","family":"van der Maarel","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000797"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2010.04.007"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006819"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182897116"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001783"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2015.08.007"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1189044"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.20001"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2014.6090"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22593"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.191"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21091"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e328357f22d"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1001181"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu251"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv315"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt314"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2012.01647.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.07.022"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007482"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.06.041"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026820"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.11.013"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12109"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038779"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-010-9474-6"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)92148-B"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.28.10.655"},{"key":"e_1_2_10_30_1","unstructured":"PadbergGW. 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