{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T07:52:44Z","timestamp":1740124364811,"version":"3.37.3"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,6,11]],"date-time":"2018-06-11T00:00:00Z","timestamp":1528675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/01067"],"award-info":[{"award-number":["PI17\/01067"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:p><jats:italic>FMR1<\/jats:italic> premutation carriers (55\u2010200 CGGs) are at risk of developing Fragile X\u2010associated primary ovarian insufficiency as well as Fragile X\u2010associated tremor\/ataxia syndrome. <jats:italic>FMR1<\/jats:italic> premutation alleles are also associated with a variety of disorders, including psychiatric, developmental, and neurological problems. However, there is a major concern regarding clinical implications of smaller CGG expansions known as intermediate alleles (IA) or gray zone alleles (45\u201054 CGG). Although several studies have hypothesized that IA may be involved in the etiology of <jats:italic>FMR1<\/jats:italic> premutation associated phenotypes, this association still remains unclear. The aim of this study was to provide new data on the clinical implications of IA. We reviewed a total of 17 011 individuals: 1142 with primary ovarian insufficiency, 478 with movement disorders, 14 006 with neurodevelopmental disorders and 1385 controls. Similar IA frequencies were detected in all the cases and controls (cases 1.20% vs controls 1.39%, <jats:italic>P<\/jats:italic> = .427). When comparing the allelic frequencies of IA \u2265 50CGGs, a greater, albeit not statistically significant, number of alleles were detected in all the cohorts of patients. Therefore, IA below 50 CGGs should not be considered as risk factors for <jats:italic>FMR1<\/jats:italic> premutation\u2010associated phenotypes, at least in our population. However, the clinical implication of IA \u2265 50CGGs remains to be further elucidated.<\/jats:p>","DOI":"10.1111\/cge.13257","type":"journal-article","created":{"date-parts":[[2018,3,31]],"date-time":"2018-03-31T15:24:04Z","timestamp":1522509844000},"page":"153-158","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical implication of <i>FMR1<\/i> intermediate alleles in a Spanish population"],"prefix":"10.1111","volume":"94","author":[{"given":"M.I.","family":"Alvarez\u2010Mora","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic  Barcelona Spain"},{"name":"Institut d'Investigaci\u00f3 Biom\u00e8dica August Pi I Sunyer IDIBAPS  Barcelona Spain"},{"name":"Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Madrigal","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic  Barcelona Spain"},{"name":"Institut d'Investigaci\u00f3 Biom\u00e8dica August Pi I Sunyer IDIBAPS  Barcelona Spain"},{"name":"Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Genetics Unit Hospital Universitario y Politecnico La Fe  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.\u2010I.","family":"Tejada","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII  Valencia Spain"},{"name":"Molecular Genetics Laboratory, Genetics Service Cruces University Hospital  Barakaldo Spain"},{"name":"Biocruces Health Research Institute  Barakaldo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Izquierdo\u2010Alvarez","sequence":"additional","affiliation":[{"name":"Genetics department of Clinical Biochemistry Service University Hospital Miguel Servet  Zaragoza Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Sanchez\u2010Villar de Saz","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Caro\u2010Llopis","sequence":"additional","affiliation":[{"name":"Genetics Unit Hospital Universitario y Politecnico La Fe  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O.","family":"Villate","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory, Genetics Service Cruces University Hospital  Barakaldo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Rodr\u00edguez\u2010Santiago","sequence":"additional","affiliation":[{"name":"qGenomics (Quantitative Genomic Medicine Laboratories)  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.A.","family":"P\u00e9rez Jurado","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII  Valencia Spain"},{"name":"Genetics Unit, Universitat Pompeu Fabra, and Hospital del Mar Research Institute (IMIM)  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Rodriguez\u2010Revenga","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic  Barcelona Spain"},{"name":"Institut d'Investigaci\u00f3 Biom\u00e8dica August Pi I Sunyer IDIBAPS  Barcelona Spain"},{"name":"Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7906-0916","authenticated-orcid":false,"given":"M.","family":"Mil\u00e0","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic  Barcelona Spain"},{"name":"Institut d'Investigaci\u00f3 Biom\u00e8dica August Pi I Sunyer IDIBAPS  Barcelona Spain"},{"name":"Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,6,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31818c2606"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/gm401"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.2353\/jmoldx.2009.080174"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/340846"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.106"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.14.1449"},{"key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"208","DOI":"10.5334\/tohm.233","article-title":"In the gray zone in the fragile X gene: what are the key unanswered clinical and biological questions?","volume":"4","author":"Hall DA","year":"2014","journal-title":"Tremor Other Hyperkinet Mov"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.41"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-5434-2_6"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.24021"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12026"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990528)84:3<198::AID-AJMG5>3.0.CO;2-W"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.20030"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32990"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-005-1326-8"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dei432"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2008.04.037"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2009.01275.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12070"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deq058"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2015.03.027"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32065"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes7120123"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/der168"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2013.64"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deu095"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2010.12.013"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.13257","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13257","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T16:20:55Z","timestamp":1695486055000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.13257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,11]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["10.1111\/cge.13257"],"URL":"https:\/\/doi.org\/10.1111\/cge.13257","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"type":"print","value":"0009-9163"},{"type":"electronic","value":"1399-0004"}],"subject":[],"published":{"date-parts":[[2018,6,11]]},"assertion":[{"value":"2018-02-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}