{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:28:21Z","timestamp":1790774901736,"version":"4.1.0"},"reference-count":106,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PRIN","award":["201789LFKB"],"award-info":[{"award-number":["201789LFKB"]}]},{"name":"PRIN","award":["D.1-2020"],"award-info":[{"award-number":["D.1-2020"]}]},{"name":"MIUR-University","award":["201789LFKB"],"award-info":[{"award-number":["201789LFKB"]}]},{"name":"MIUR-University","award":["D.1-2020"],"award-info":[{"award-number":["D.1-2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A dynamic mutation in exon 1 of the FMR1 gene causes Fragile X-related Disorders (FXDs), due to the expansion of an unstable CGG repeat sequence. Based on the CGG sequence size, two types of FMR1 alleles are possible: \u201cpremutation\u201d (PM, with 56-200 CGGs) and \u201cfull mutation\u201d (FM, with &gt;200 triplets). Premutated females are at risk of transmitting a FM allele that, when methylated, epigenetically silences FMR1 and causes Fragile X syndrome (FXS), a very common form of inherited intellectual disability (ID). Expansions events of the CGG sequence are predominant over contractions and are responsible for meiotic and mitotic instability. The CGG repeat usually includes one or more AGG interspersed triplets that influence allele stability and the risk of transmitting FM to children through maternal meiosis. A unique mechanism responsible for repeat instability has not been identified, but several processes are under investigations using cellular and animal models. The formation of unusual secondary DNA structures at the expanded repeats are likely to occur and contribute to the CGG expansion. This review will focus on the current knowledge about CGG repeat instability addressing the CGG sequence expands.<\/jats:p>","DOI":"10.3390\/ijms23105425","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T21:46:53Z","timestamp":1652392013000},"page":"5425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Mechanisms of the FMR1 Repeat Instability: How Does the CGG Sequence Expand?"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4707-2242","authenticated-orcid":false,"given":"Elisabetta","family":"Tabolacci","sequence":"first","affiliation":[{"name":"Dipartimento Scienze della Vita e Sanit\u00e0 Pubblica, Sezione di Medicina Genomica, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Nobile","sequence":"additional","affiliation":[{"name":"Dipartimento Scienze della Vita e Sanit\u00e0 Pubblica, Sezione di Medicina Genomica, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Pucci","sequence":"additional","affiliation":[{"name":"Dipartimento Scienze della Vita e Sanit\u00e0 Pubblica, Sezione di Medicina Genomica, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5104-1521","authenticated-orcid":false,"given":"Pietro","family":"Chiurazzi","sequence":"additional","affiliation":[{"name":"Dipartimento Scienze della Vita e Sanit\u00e0 Pubblica, Sezione di Medicina Genomica, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"},{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/nrg1689","article-title":"Repeat instability: Mechanisms of dynamic mutations","volume":"6","author":"Pearson","year":"2005","journal-title":"Nat. Rev. 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