{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T23:56:38Z","timestamp":1787874998971,"version":"build-2784847793"},"reference-count":119,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T00:00:00Z","timestamp":1734739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fragile X syndrome (FXS) is a genetic condition caused by the inheritance of alleles with &gt;200 CGG repeats in the 5\u2032 UTR of the fragile X messenger ribonucleoprotein 1 (FMR1) gene. These full mutation (FM) alleles are associated with DNA methylation and gene silencing, which result in intellectual disabilities, developmental delays, and social and behavioral issues. Mosaicism for both the size of the CGG repeat tract and the extent of its methylation is commonly observed in individuals with the FM. Mosaicism has also been reported in carriers of premutation (PM) alleles, which have 55\u2013200 CGG repeats. PM alleles confer risk for the fragile X premutation-associated conditions (FXPAC), including FXTAS, FXPOI, and FXAND, conditions thought to be due to the toxic consequences of transcripts containing large CGG-tracts. Unmethylated FM (UFM) alleles are transcriptionally and translationally active. Thus, they produce transcripts with toxic effects. These transcripts do produce some FMRP, the encoded product of the FMR1 gene, albeit with reduced translational efficiency. As a result, mosaicism can result in a complex clinical presentation. Here, we review the concept of mosaicism in both FXS and in PM carriers, including its potential clinical significance.<\/jats:p>","DOI":"10.3390\/ijms252413681","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T02:39:56Z","timestamp":1734921596000},"page":"13681","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Somatic Instability Leading to Mosaicism in Fragile X Syndrome and Associated Disorders: Complex Mechanisms, Diagnostics, and Clinical Relevance"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2137-5405","authenticated-orcid":false,"given":"Dragana","family":"Protic","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Fragile X Clinic, Special Hospital for Cerebral Palsy and Developmental Neurology, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7169-7111","authenticated-orcid":false,"given":"Roberta","family":"Polli","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Padova, 35127 Padova, Italy"},{"name":"Pediatric Research Institute Citt\u00e0 della Speranza, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Bettella","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Padova, 35127 Padova, Italy"},{"name":"Pediatric Research Institute Citt\u00e0 della Speranza, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Usdin","sequence":"additional","affiliation":[{"name":"Laboratory of Cell and Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6788-0653","authenticated-orcid":false,"given":"Alessandra","family":"Murgia","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Padova, 35127 Padova, Italy"},{"name":"Pediatric Research Institute Citt\u00e0 della Speranza, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6388-9180","authenticated-orcid":false,"given":"Flora","family":"Tassone","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, CA 95817, USA"},{"name":"Medical Investigation of Neurodevelopmental Disorders (MIND) Institute UCDH, University of California Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1034\/j.1399-0004.2000.580504.x","article-title":"The causes and consequences of random and non-random X chromosome inactivation in humans","volume":"58","author":"Brown","year":"2000","journal-title":"Clin. 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