{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FRG2 is a gene mapping in close proximity to the D4Z4 repeat array on chromosome 4 (and its homologous copy on chromosome 10) that has emerged as a candidate contributor to the pathogenesis of facioscapulohumeral muscular dystrophy (FSHD). Although bioinformatic analyses have not revealed clearly defined functional motifs in the predicted protein, experimental studies indicate that the FRG2 promoter is highly active and subject to inhibition by increasing numbers of D4Z4 repeat units. In normal development, FRG2 expression is barely detectable; however, in FSHD patient–derived myoblasts undergoing differentiation, low but distinct levels of FRG2 are observed, suggesting that deregulation of its expression may involve altered chromatin organization of the 4q35 region. Furthermore, the FRG2 promoter is responsive to myogenic regulators—for example, activation of the D4Z4 enhancer by KLF15 leads to upregulation of FRG2—as well as to factors that might act downstream of DUX4, the aberrantly expressed double homeobox transcription factor in FSHD. Notably, transient expression experiments have demonstrated that the FRG2 protein localizes to the nucleus and that its overexpression provokes diverse morphological changes, thus implicating it in processes potentially linked to myogenesis. Despite its misexpression in FSHD, overexpression of FRG2 in transgenic mouse models does not lead to a muscular dystrophy phenotype, suggesting that its contribution to disease may be as part of a multifactorial pathogenic cascade rather than as a sole causative factor."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "T Rijkers, G Deidda, S van Koningsbruggen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FRG2, an FSHD candidate gene, is transcriptionally upregulated in differentiating primary myoblast cultures of FSHD patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2004.019364"}], "href": "https://doi.org/10.1136/jmg.2004.019364"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15520407"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15520407"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Petr Dmitriev, Andrei Petrov, Eugenie Ansseau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Krüppel-like factor 15 as a molecular link between myogenic factors and a chromosome 4q transcriptional enhancer implicated in facioscapulohumeral dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.254052"}], "href": "https://doi.org/10.1074/jbc.M111.254052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21937448"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21937448"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Rinse Klooster, Kirsten Straasheijm, Bharati Shah, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comprehensive expression analysis of FSHD candidate genes at the mRNA and protein level."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2009.62"}], "href": "https://doi.org/10.1038/ejhg.2009.62"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19809486"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19809486"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Gefei Xiao, Xianrong Qiu, Yuqiu Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prenatal diagnosis of a 4.5-Mb deletion at chromosome 4q35.1q35.2: Case report and literature review."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cytogenet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13039-021-00573-y"}], "href": "https://doi.org/10.1186/s13039-021-00573-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34794455"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34794455"}]}]}]}