{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:12:32Z","timestamp":1792066352205,"version":"4.4.0"},"reference-count":97,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,1,24]],"date-time":"2021-01-24T00:00:00Z","timestamp":1611446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100010553","name":"MIND Institute, University of California, Davis","doi-asserted-by":"publisher","award":["the International Training Program for Neurodevelopmental Disorders (ITPND)"],"award-info":[{"award-number":["the International Training Program for Neurodevelopmental Disorders (ITPND)"]}],"id":[{"id":"10.13039\/100010553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["NICHD HD036071"],"award-info":[{"award-number":["NICHD HD036071"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Fragile X syndrome (FXS) is the most common single gene disorder, which causes autism and intellectual disability. The fragile X mental retardation 1 (\n                    <jats:italic>FMR1<\/jats:italic>\n                    ) gene is silenced when cytosine\u2010guanine\u2010guanine (CGG) triplet repeats exceed 200, which is the full mutation that causes FXS. Carriers of FXS have a CGG repeat between 55 and 200, which is defined as a premutation and transcription of the gene is overactive with high levels of the\n                    <jats:italic>FMR1<\/jats:italic>\n                    mRNA. Most carriers of the premutation have normal levels of fragile X mental retardation protein (FMRP) and a normal intelligence, but in the upper range of the premutation (120\u2013200) the FMRP level may be lower than normal. The clinical problems associated with the premutation are caused by the RNA toxicity associated with increased\n                    <jats:italic>FMR1<\/jats:italic>\n                    mRNA levels, although for some mildly lowered FMRP can cause problems associated with FXS. The RNA toxicity causes various health problems in the carriers including but not limited to fragile X\u2010associated tremor\/ataxia syndrome, fragile X\u2010associated primary ovarian insufficiency, and fragile X\u2010associated neuropsychiatric disorders. Since some individuals with neuropsychiatric problems do not meet the severity for a diagnosis of a \u201cdisorder\u201d then the condition can be labeled as fragile X premutation associated condition (FXPAC). Physicians must be able to recognize these health problems in the carriers and provide appropriate management.\n                  <\/jats:p>","DOI":"10.1111\/cge.13924","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T14:00:25Z","timestamp":1610719225000},"page":"751-760","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Fragile X premutation and associated health conditions: A review"],"prefix":"10.1111","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9888-0565","authenticated-orcid":false,"given":"Nattaporn","family":"Tassanakijpanich","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine Prince of Songkla University  Songkhla Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randi J.","family":"Hagerman","sequence":"additional","affiliation":[{"name":"UC Davis MIND Institute UC Davis Health  Sacramento California USA"},{"name":"Department of Pediatrics University of California, Davis, School of Medicine  Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juthamas","family":"Worachotekamjorn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine Prince of Songkla University  Songkhla Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,24]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"GeneReviews","author":"Hunter JE","year":"1998"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36511"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2019-3211"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32065"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90397-H"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2020.00266"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2016.82"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1866-1955-6-26"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2018.00564"},{"key":"e_1_2_11_11_1","first-page":"1000119","article-title":"Molecular advances leading to treatment implications for fragile X premutation carriers","volume":"3","author":"Polussa J","year":"2014","journal-title":"Brain Disord Ther"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61165"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1866-1955-6-24"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1866-1955-6-27"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32439"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1037\/0894-4105.17.4.646"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1866-1955-6-28"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32203"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1866-1955-6-29"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-016-9171-8"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004703-200604002-00012"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.5582\/irdr.2015.01029"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.09m05407blu"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1037\/a0026528"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2015.07.015"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp0808697"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12905-018-0665-2"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deg005"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.2217\/WHE.14.82"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12921"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh635"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.51"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/13.5.1184"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jogoh.2019.04.007"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103316"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dem148"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/GME.0000000000000658"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00290"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201510"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200451"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.3109\/13697137.2015.1094784"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.57.1.127"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-016-0799-4"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.042374"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-010-0270-5"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.4.460"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21493"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000045"},{"issue":"10","key":"e_1_2_11_49_1","first-page":"1757","article-title":"Fragile X premutation carriers: characteristic MR imaging findings of adult male patients with progressive cerebellar and cognitive dysfunction","volume":"23","author":"Brunberg JA","year":"2002","journal-title":"AJNR Am J Neuroradiol"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1086\/374321"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000269781.10417.7b"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.12449"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00695"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00379"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70125-X"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/1866-1955-6-31"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32060"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-016-0805-x"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35569"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.31237"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.2632"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12109"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-011-1106-6"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.5582\/irdr.2014.01023"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-102021"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrdd.20006"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0226811"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.10099"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1086\/302720"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.14.1449"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.280807"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dev280"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0860-9"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hox007"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1989.tb03804.x"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.13m08546"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep21719"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-017-0555-6"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0225191"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00512"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2014.12.015"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20091960"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320230119"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.282834"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.59.10.1541"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.27443"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756285611406166"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.12793\/tcp.2019.27.3.92"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2011-101803"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000001948"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1024"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.1815"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.4808"},{"key":"e_1_2_11_94_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2016-1159H"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e3181fae884"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.GIM.0000182468.22666.dd"},{"key":"e_1_2_11_97_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2011.01723.x"},{"key":"e_1_2_11_98_1","doi-asserted-by":"publisher","DOI":"10.1186\/1866-1955-6-25"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13924","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.13924","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13924","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T11:48:36Z","timestamp":1693568916000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.13924"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,24]]},"references-count":97,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1111\/cge.13924"],"URL":"https:\/\/doi.org\/10.1111\/cge.13924","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.13924\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13924\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13924\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13924\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13924\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13924\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13924\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13924\/v1\/review2","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,24]]},"assertion":[{"value":"2020-11-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}