{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T17:17:50Z","timestamp":1775495870718,"version":"3.50.1"},"reference-count":209,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T00:00:00Z","timestamp":1628035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CP15\/00180, CPII20\/00025, PI16\/00722, PI19\/00125"],"award-info":[{"award-number":["CP15\/00180, CPII20\/00025, PI16\/00722, PI19\/00125"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Abnormal trinucleotide expansions cause rare disorders that compromise quality of life and, in some cases, lifespan. In particular, the expansions of the CGG-repeats stretch at the 5\u2019-UTR of the Fragile X Mental Retardation 1 (FMR1) gene have pleiotropic effects that lead to a variety of Fragile X-associated syndromes: the neurodevelopmental Fragile X syndrome (FXS) in children, the late-onset neurodegenerative disorder Fragile X-associated tremor-ataxia syndrome (FXTAS) that mainly affects adult men, the Fragile X-associated primary ovarian insufficiency (FXPOI) in adult women, and a variety of psychiatric and affective disorders that are under the term of Fragile X-associated neuropsychiatric disorders (FXAND). In this review, we will describe the pathological mechanisms of the adult \u201cgain-of-function\u201d syndromes that are mainly caused by the toxic actions of CGG RNA and FMRpolyG peptide. There have been intensive attempts to identify reliable peripheral biomarkers to assess disease progression and onset of specific pathological traits. Mitochondrial dysfunction, altered miRNA expression, endocrine system failure, and impairment of the GABAergic transmission are some of the affectations that are susceptible to be tracked using peripheral blood for monitoring of the motor, cognitive, psychiatric and reproductive impairment of the CGG-expansion carriers. We provided some illustrative examples from our own cohort. Understanding the association between molecular pathogenesis and biomarkers dynamics will improve effective prognosis and clinical management of CGG-expansion carriers.<\/jats:p>","DOI":"10.3390\/ijms22168368","type":"journal-article","created":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T08:47:52Z","timestamp":1628066872000},"page":"8368","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1229-0565","authenticated-orcid":false,"given":"Luis M.","family":"Valor","sequence":"first","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL), 03010 Alicante, Spain"},{"name":"Laboratorio de Apoyo a la Investigaci\u00f3n, Hospital General Universitario de Alicante, Av. Pintor Baeza 12, 03010 Alicante, Spain"},{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n Biom\u00e9dica de C\u00e1diz (INiBICA), 11009 C\u00e1diz, Spain"},{"name":"Unidad de Investigaci\u00f3n, Hospital Universitario Puerta del Mar, Av. Ana de Viya 21, 11009 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge C.","family":"Morales","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n Biom\u00e9dica de C\u00e1diz (INiBICA), 11009 C\u00e1diz, Spain"},{"name":"Unidad de Investigaci\u00f3n, Hospital Universitario Puerta del Mar, Av. Ana de Viya 21, 11009 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3991-4147","authenticated-orcid":false,"given":"Irati","family":"Herv\u00e1s-Corpi\u00f3n","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n Biom\u00e9dica de C\u00e1diz (INiBICA), 11009 C\u00e1diz, Spain"},{"name":"Unidad de Investigaci\u00f3n, Hospital Universitario Puerta del Mar, Av. Ana de Viya 21, 11009 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosario","family":"Mar\u00edn","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n Biom\u00e9dica de C\u00e1diz (INiBICA), 11009 C\u00e1diz, Spain"},{"name":"Unidad de Gen\u00e9tica, Hospital Universitario Puerta del Mar, Av. Ana de Viya 21, 11009 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1002\/ajmg.a.36241","article-title":"Fragile X syndrome: From protein function to therapy","volume":"161A","author":"Bagni","year":"2013","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/ejhg.2011.41","article-title":"Intermediate FMR1 alleles and cognitive and\/or behavioural phenotypes","volume":"19","author":"Madrigal","year":"2011","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1002\/mds.28086","article-title":"Fragile X gray zone alleles are associated with signs of parkinsonism and earlier death","volume":"35","author":"Hall","year":"2020","journal-title":"Mov. 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