{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:11:57Z","timestamp":1791241917368,"version":"4.1.0"},"reference-count":102,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,5,25]],"date-time":"2024-05-25T00:00:00Z","timestamp":1716595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"NICHD","doi-asserted-by":"publisher","award":["HD036071"],"award-info":[{"award-number":["HD036071"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"NICHD","doi-asserted-by":"publisher","award":["P50 HD103526"],"award-info":[{"award-number":["P50 HD103526"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Azrieli Foundation","award":["HD036071"],"award-info":[{"award-number":["HD036071"]}]},{"name":"Azrieli Foundation","award":["P50 HD103526"],"award-info":[{"award-number":["P50 HD103526"]}]},{"name":"Tides Foundation","award":["HD036071"],"award-info":[{"award-number":["HD036071"]}]},{"name":"Tides Foundation","award":["P50 HD103526"],"award-info":[{"award-number":["P50 HD103526"]}]},{"name":"Victor LaFave III Fund","award":["HD036071"],"award-info":[{"award-number":["HD036071"]}]},{"name":"Victor LaFave III Fund","award":["P50 HD103526"],"award-info":[{"award-number":["P50 HD103526"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Fragile X syndrome (FXS) is a genetic disorder caused by a mutation in the fragile X messenger ribonucleoprotein 1 (FMR1) gene and known to be a leading cause of inherited intellectual disability globally. It results in a range of intellectual, developmental, and behavioral problems. Fragile X premutation-associated conditions (FXPAC), caused by a smaller CGG expansion (55 to 200 CGG repeats) in the FMR1 gene, are linked to other conditions that increase morbidity and mortality for affected persons. Limited research has been conducted on the burden, characteristics, diagnosis, and management of these conditions in Africa. This comprehensive review provides an overview of the current literature on FXS and FXPAC in Africa. The issues addressed include epidemiology, clinical features, discrimination against affected persons, limited awareness and research, and poor access to resources, including genetic services and treatment programs. This paper provides an in-depth analysis of the existing worldwide data for the diagnosis and treatment of fragile X disorders. This review will improve the understanding of FXS and FXPAC in Africa by incorporating existing knowledge, identifying research gaps, and potential topics for future research to enhance the well-being of individuals and families affected by FXS and FXPAC.<\/jats:p>","DOI":"10.3390\/genes15060683","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T10:14:07Z","timestamp":1716804847000},"page":"683","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Comprehensive Review of Fragile X Syndrome and Fragile X Premutation Associated Conditions in Africa"],"prefix":"10.3390","volume":"15","author":[{"given":"Chioma N. P.","family":"Mbachu","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Faculty of Medicine, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Nnewi 435101, Nigeria"},{"name":"MIND Institute, University of California Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikechukwu Innocent","family":"Mbachu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Faculty of Medicine, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Nnewi 435101, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5029-8448","authenticated-orcid":false,"given":"Randi","family":"Hagerman","sequence":"additional","affiliation":[{"name":"MIND Institute, University of California Davis, Sacramento, CA 95817, USA"},{"name":"Department of Pediatrics, University of California Davis Health, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1136\/jnnp.6.3-4.154","article-title":"A pedigree of mental defect showing sex-linkage","volume":"6","author":"Martin","year":"1943","journal-title":"J. Neurol. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/0092-8674(91)90397-H","article-title":"Identification of a Gene (HIM?-1) Containing a CGG Repeat Coincident with a Breakpoint Cluster Region Exhibiting Length Variation in Fragile X Syndrome","volume":"65","author":"Verkerk","year":"1991","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.yapd.2009.08.008","article-title":"Fragile X: A Family of Disorders","volume":"56","author":"Chonchaiya","year":"2009","journal-title":"Adv. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4314","DOI":"10.1172\/JCI63141","article-title":"Fragile X syndrome: Causes, diagnosis, mechanisms, and therapeutics","volume":"122","author":"Bagni","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s11689-011-9074-7","article-title":"Targeted treatments for fragile X syndrome","volume":"3","author":"Knox","year":"2011","journal-title":"J. Neurodev. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.molmed.2010.08.005","article-title":"Potential therapeutic interventions for fragile X syndrome","volume":"16","author":"Levenga","year":"2010","journal-title":"Trends Mol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hagerman Randi, J., and Hagerman Paul, J. (2020). Fragile X Syndrome and Premutation Disorders Clinics in Developmental Medicine Fragile X Syndrome and Premutation Disorders New Developments and Treatments, Mac Keith Press.","DOI":"10.1002\/9781119432692.ch28"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/npp.2011.137","article-title":"Therapeutic strategies in fragile X syndrome: Dysregulated mGluR signaling and be-yond","volume":"37","author":"Gross","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"216","DOI":"10.2174\/138920211795677886","article-title":"Fragile X Syndrome","volume":"12","author":"Mclennan","year":"2011","journal-title":"Curr. Genom."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"324","DOI":"10.2353\/jmoldx.2009.080173","article-title":"Screening for Expanded Alleles of the FMR1 Gene in Blood Spots from Newborn Males in a Spanish Population","volume":"11","author":"Walichiewicz","year":"2009","journal-title":"J. Mol. Diagn."},{"key":"ref_11","unstructured":"Hagerman, R.J., and Hagerman, P.J. (2002). Outcomes in Neurodevelopmental and Genetic Disorders, Cambridge University Press. Available online: https:\/\/www.cambridge.org\/core\/product\/identifier\/CBO9780511543876A015\/type\/book_part."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1093\/hmg\/2.10.1659","article-title":"High resolution methylation analysis of the FMR1 gene trinucleotide repeat region in fragile X syndrome","volume":"2","author":"Hornstra","year":"1993","journal-title":"Hum. Mol. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/mrdd.10084","article-title":"Auditory Neuropathy\/Dys-Synchrony: Diagnosis and Management","volume":"9","author":"Berlin","year":"2003","journal-title":"Ment. Retard. Dev. Disabil. Res. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tassone, F., Protic, D., Allen, E.G., Archibald, A.D., Baud, A., Brown, T.W., Budimirovic, D.B., Cohen, J., Dufour, B., and Eiges, R. (2023). Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation. Cells, 12.","DOI":"10.3390\/cells12182330"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nrdp.2017.65","article-title":"Fragile X syndrome","volume":"3","author":"Hagerman","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.ajhg.2009.09.007","article-title":"Incidence of Fragile X Syndrome by Newborn Screening for Methylated FMR1 DNA","volume":"85","author":"Coffee","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/j.1399-0004.2009.01237.x","article-title":"Screening and instability of FMR1 alleles in a prospective sample of 24,449 mother-newborn pairs from the general population","volume":"76","author":"Levesque","year":"2009","journal-title":"Clin Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1002\/ajmg.a.36511","article-title":"Epidemiology of fragile X syndrome: A systematic review and meta-analysis","volume":"164","author":"Hunter","year":"2014","journal-title":"Am. J. Med Genet. Part A"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tassone, F., and Hall, D.A. (2016). FXTAS, FXPOI, and Other Premutation Disorders, Springer. [2nd ed.].","DOI":"10.1007\/978-3-319-33898-9"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"994","DOI":"10.7196\/SAMJ.7144","article-title":"Diagnostic, carrier and prenatal genetic testing for fragile X syndrome and other FMR-1-related disorders in Johannesburg, South Africa: A 20-year review","volume":"103","author":"Essop","year":"2013","journal-title":"South Afr. Med. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e399","DOI":"10.1016\/j.ejmg.2011.03.013","article-title":"Initiation of a medical genetics service in sub-Saharan Africa: Experience of prenatal diagnosis in Cameroon","volume":"54","author":"Wonkam","year":"2011","journal-title":"Eur. J. Med. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"259","DOI":"10.18388\/abp.2014_1893","article-title":"Simple molecular diagnostic method for Fragile X syn-drome in Egyptian patients: Pilot study","volume":"61","author":"Meguid","year":"2014","journal-title":"Acta Biochimica Polonica"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1111\/j.1469-1809.2010.00582.x","article-title":"Genetic Diversity of the Fragile X Syndrome Gene (FMR1) in a Large Sub-Saharan West African Population","volume":"74","author":"Peprah","year":"2010","journal-title":"Ann. Hum. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/(SICI)1096-8628(19960712)64:1<216::AID-AJMG39>3.0.CO;2-O","article-title":"Extended Gene Diversity at the FMRl Locus and Neighbouring CA Repeats in a Sub-Saharan Population","volume":"64","author":"Chiurazzi","year":"1996","journal-title":"Am. J. Med. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1136\/jmg.35.10.878","article-title":"Molecular evidence that fragile X syndrome occurs in the South African black population","volume":"35","author":"Goldman","year":"1998","journal-title":"J. Med. Genet."},{"key":"ref_26","unstructured":"Abdel Meguid, N., and El Awady, M.K. (2024, March 23). Prevalence of Fragile X Syndrome among School-Age Egyptian Males. Available online: https:\/\/www.researchgate.net\/publication\/285380905."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1002\/jgc4.1440","article-title":"Explanatory models for the cause of Fragile X Syndrome in rural Cameroon","volume":"30","author":"Kamga","year":"2021","journal-title":"J. Genet. Couns."},{"key":"ref_28","first-page":"1123","article-title":"Fragile X allelemorphism among the mentally retarded and in affected families","volume":"4","author":"Latunji","year":"2009","journal-title":"Sci. Res. Essay"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.fertnstert.2006.09.004","article-title":"The FMR1 premutation and reproduction","volume":"87","author":"Wittenberger","year":"2007","journal-title":"Fertil. Steril."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/gepi.20329","article-title":"Fragile X-associated primary ovarian insufficiency: Evidence for additional genetic contributions to severity","volume":"32","author":"Hunter","year":"2008","journal-title":"Genet. Epidemiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1093\/hmg\/10.14.1449","article-title":"Reduced FMRP and increased FMR1 transcription is proportionally asso-ciated with CGG repeat number in intermediate-length and premutation carriers","volume":"10","author":"Kenneson","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s00439-004-1086-x","article-title":"A study of the distributional characteristics of FMR1 transcript levels in 238 individuals","volume":"114","author":"He","year":"2004","journal-title":"Hum. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1086\/302720","article-title":"Elevated Levels of FMR1 mRNA in Carrier Males: A New Mechanism of Involvement in the Fragile-X Syndrome","volume":"66","author":"Tassone","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/ejhg.2014.185","article-title":"EMQN best practice guidelines for the molecular genetic testing and re-porting of fragile X syndrome and other fragile X-associated disorders","volume":"23","author":"Biancalana","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/S0959-437X(02)00299-X","article-title":"The fragile X premutation: Into the phenotypic fold","volume":"12","author":"Hagerman","year":"2002","journal-title":"Curr. Opin. Genet Dev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1136\/jmg.2008.059055","article-title":"The fragile X prevalence paradox","volume":"45","author":"Hagerman","year":"2008","journal-title":"J. Med. Genet."},{"key":"ref_37","first-page":"283","article-title":"Fragile X Checklist","volume":"38","author":"Hagerman","year":"1991","journal-title":"J. Med. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/MCD.0000000000000471","article-title":"Fragile X syndrome in Democratic Republic of Congo: Dysmorphic, cognitive and behavioral findings in 14 subjects from three families","volume":"33","author":"Lubala","year":"2023","journal-title":"Clin. Dysmorphol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/j.jocn.2008.12.018","article-title":"Assessment of a clinical checklist in the di-agnosis of fragile X syndrome in India","volume":"16","author":"Guruju","year":"2009","journal-title":"J. Clin. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1352\/0047-6765(2000)038<0207:PCTSFF>2.0.CO;2","article-title":"Phenotypic Checklist to Screen for Fragile X Syndrome in People With Mental Retardation","volume":"38","author":"Maes","year":"2000","journal-title":"Ment. Retard."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.ando.2015.10.001","article-title":"Analysis of FMR1 gene premutation and X chromo-some cytogenetic abnormalities in 100 Tunisian patients presenting premature ovarian failure","volume":"76","author":"Bouali","year":"2015","journal-title":"Ann. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1080\/13697137.2022.2153033","article-title":"The global prevalence of premature ovarian insufficiency: A systematic review and meta-analysis","volume":"26","author":"Li","year":"2023","journal-title":"Climacteric"},{"key":"ref_43","unstructured":"Sopiarz, N., and Sparzak, P.B. (2024, March 24). Primary Ovarian Insufficiency, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK589674\/."},{"key":"ref_44","first-page":"196","article-title":"Premature ovarian failure","volume":"68","author":"Goswami","year":"2007","journal-title":"Horm. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1002\/(SICI)1096-8628(19991229)89:4<186::AID-AJMG3>3.0.CO;2-5","article-title":"Ovarian differentiation and gonadal failure","volume":"89","author":"Simpson","year":"1999","journal-title":"Am. J. Med. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1677\/JME-10-0070","article-title":"Genes involved in human premature ovarian failure","volume":"45","author":"Persani","year":"2010","journal-title":"J. Mol. Endocrinol."},{"key":"ref_47","unstructured":"Zinn, A.R., and Ross, J.L. (2024, March 25). Turner Syndrome and Haploinsufficiency. Available online: http:\/\/biomednet.com\/elecref\/0959437X00800322."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/1096-8628(200023)97:3<189::AID-AJMG1036>3.0.CO;2-J","article-title":"Premature ovarian failure in the fragile X syndrome","volume":"97","author":"Sherman","year":"2000","journal-title":"Am. J. Med. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1093\/humrep\/dem148","article-title":"Examination of reproductive aging milestones among women who carry the FMR1premutation","volume":"22","author":"Allen","year":"2007","journal-title":"Hum. Reprod."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1002\/ajmg.b.32065","article-title":"Prevalence of CGG expansions of the FMR1 gene in a US population-based sample","volume":"159B","author":"Seltzer","year":"2012","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_51","first-page":"1648","article-title":"Refining the risk for fragile X\u2013associated primary ovarian insufficiency (FXPOI) by FMR1 CGG repeat size","volume":"23","author":"Allen","year":"2021","journal-title":"Anesthesia Analg."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1097\/GME.0000000000000658","article-title":"Reproductive and gynecologic care of women with fragile X primary ovarian insufficiency (FXPOI)","volume":"23","author":"Hipp","year":"2016","journal-title":"Menopause"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/ajmg.1320380221","article-title":"Heterozygous fragile X female: Historical, physical, cognitive, and cytogenetic features","volume":"38","author":"Cronister","year":"1991","journal-title":"Am. J. Med. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1055\/s-2000-13476","article-title":"Premature Ovarian Failure and the FMR1 Gene","volume":"18","author":"Murray","year":"2000","journal-title":"Semin. Reprod. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1002\/ajmg.b.32277","article-title":"Curvilinear association of CGG repeats and age at menopause in women with FMR1 premutation expansions","volume":"165","author":"Mailick","year":"2014","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1093\/humrep\/deh635","article-title":"Association of FMR1 repeat size with ovarian dysfunction","volume":"20","author":"Sullivan","year":"2005","journal-title":"Hum. Reprod."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s11427-012-4355-2","article-title":"An update on primary ovarian insufficiency","volume":"55","author":"Jin","year":"2012","journal-title":"Sci. China Life Sci."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Archibald, A.D., McClaren, B.J., Caruana, J., Tutty, E., King, E.A., Halliday, J.L., Best, S., Kanga-Parabia, A., Bennetts, B.H., and Cliffe, C.C. (2022). The Australian Reproductive Genetic Carrier Screening Project (Mackenzie\u2019s Mission): Design and Implementation. J. Pers. Med., 12.","DOI":"10.3390\/jpm12111781"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"652","DOI":"10.3389\/fnins.2018.00652","article-title":"Fragile X-Associated Disorders in Serbia: Baseline Quantitative and Qualitative Survey of Knowledge, Attitudes and Practices Among Medical Professionals","volume":"12","author":"Budimirovic","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1002\/ajmg.a.35674","article-title":"\u201cIt\u2019s about having the choice\u201d: Stakeholder percep-tions of population-based genetic carrier screening for fragile X syndrome","volume":"161","author":"Archibald","year":"2013","journal-title":"Am. J. Med. Genet A"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1002\/ajmg.a.33122","article-title":"\u201cIt\u2019s something I need to consider\u201d: Decisions about carrier screening for fragile X syndrome in a population of non-pregnant women","volume":"149","author":"Archibald","year":"2009","journal-title":"Am. J. Med. Genet A"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/GIM.0b013e3181fa9fad","article-title":"FMR1 premutation carrier frequency in patients undergoing routine population-based carrier screening: Insights into the prevalence of fragile X syndrome, fragile X-associated tremor\/ataxia syndrome, and fragile X-associated primary ovarian insufficiency in the United States","volume":"13","author":"Hantash","year":"2011","journal-title":"Genet. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.jmoldx.2019.11.002","article-title":"Validation of Fragile X Screening in the Newborn Population Using a Fit-for-Purpose FMR1 PCR Assay System","volume":"22","author":"Lee","year":"2020","journal-title":"J. Mol. Diagn."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1097\/AOG.0b013e318163be0b","article-title":"Prevalence and Instability of Fragile X Alleles Implications for Offering Fragile X Prenatal Diagnosis","volume":"111","author":"Cronister","year":"2008","journal-title":"Obstet Gynecol."},{"key":"ref_65","first-page":"1","article-title":"FMR1 CGG allele size and prevalence ascertained through newborn screening in the United States","volume":"4","author":"Tassone","year":"2013","journal-title":"Genome Med."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Hagerman, R.J., and Hagerman, P.J. (2020). Fragile X Syndrome and Premutation Disorders New Developments and Treatments, Mac Keith Press. Available online: https:\/\/www.mackeith.co.uk.","DOI":"10.1002\/9781119432692.ch28"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Hagerman, R.J., and Hagerman, P.J. (2020). Fragile X Syndrome and Premutation Disorders New Developments and Treatments, Mac Keith Press.","DOI":"10.1002\/9781119432692.ch28"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/nrneurol.2016.82","article-title":"Fragile X-associated tremor\/ataxia syndrome-features, mechanisms and management","volume":"12","author":"Hagerman","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/1866-1955-6-31","article-title":"Emerging topics in FXTAS","volume":"6","author":"Hall","year":"2014","journal-title":"J. Neurodev Disord."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.brainres.2009.12.077","article-title":"Ubiquitin-positive intranuclear inclusions in neuronal and glial cells in a mouse model of the fragile X premutation","volume":"1318","author":"Wenzel","year":"2010","journal-title":"Brain Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1093\/brain\/awh683","article-title":"Neuropathology of fragile X-associated trem-or\/ataxia syndrome (FXTAS)","volume":"129","author":"Greco","year":"2006","journal-title":"Brain"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-013-1138-1","article-title":"Fragile X-associated tremor\/ataxia syndrome (FXTAS): Pathology and mechanisms","volume":"126","author":"Hagerman","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_73","first-page":"830","article-title":"Fragile X- Associated Tremor\/Ataxia Syndrome: Clinical Phenotype, Diagnosis, and Treatment","volume":"57","author":"Leehey","year":"2009","journal-title":"J. -Vestig. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1086\/374321","article-title":"Fragile X Premutation Tremor\/Ataxia Syn-drome: Molecular, Clinical, and Neuroimaging Correlates","volume":"72","author":"Jacquemont","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"564","DOI":"10.3389\/fpsyt.2018.00564","article-title":"Fragile X-Associated Neuropsychiatric Disorders (FXAND)","volume":"9","author":"Hagerman","year":"2018","journal-title":"Front. Psychiatry"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1080\/13854046.2016.1202239","article-title":"Fragile X-associated tremor\/ataxia syndrome: Phenotypic comparisons with other movement disorders","volume":"30","author":"Robertson","year":"2016","journal-title":"Clin. Neuropsychol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2","DOI":"10.5334\/tohm.112","article-title":"Fragile X-Associated Tremor Ataxia Syndrome: The Expanding Clinical Picture, Pathophysiology, Epidemiology, and Update on Treatment","volume":"2","author":"Hall","year":"2012","journal-title":"Tremor Other Hyperkinetic Mov."},{"key":"ref_78","first-page":"19","article-title":"Neuropathic features in fragile X premutation carriers","volume":"143A","author":"Goetz","year":"2006","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1001\/archneur.64.7.1002","article-title":"Screen for Excess FMR1 Premutation Alleles Among Males With Parkinsonism","volume":"64","author":"Kraff","year":"2007","journal-title":"Arch. Neurol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1212\/WNL.57.1.127","article-title":"Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X","volume":"57","author":"Hagerman","year":"2001","journal-title":"Neurology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12883-020-01726-z","article-title":"A Chinese case of fragile X-associated tremor\/ataxia syndrome (FXTAS) with orthostatic tremor:case report and literature review on tremor in FXTAS","volume":"20","author":"Zhao","year":"2020","journal-title":"BMC Neurol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Cabal-Herrera, A.M., Tassanakijpanich, N., Salcedo-Arellano, M.J., and Hagerman, R.J. (2020). Fragile X-Associated Tremor\/Ataxia Syndrome (FXTAS): Pathophysiology and Clinical Implications. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124391"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/mds.20673","article-title":"Intrafamilial variability in fragile X-associated tremor\/ataxia syndrome","volume":"21","author":"Peters","year":"2005","journal-title":"Mov. Disord."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3389\/fgene.2014.00365","article-title":"New observations in the fragile X-associated tremor\/ataxia syndrome (FXTAS) phenotype","volume":"5","author":"Fraint","year":"2014","journal-title":"Front. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1002\/mdc3.12944","article-title":"A Case of Generalized Chorea Presenting as an Early Feature of Fragile-X Associated Tremor\/Ataxia Syn-drome","volume":"7","author":"Islam","year":"2020","journal-title":"Mov. Disord. Clin. Pract."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.2147\/PGPM.S338846","article-title":"Fragile X Premutation: Medications, Therapy and Lifestyle Advice","volume":"Volume 14","author":"Sodhi","year":"2021","journal-title":"Pharmacogenomics and Personalized Medicine"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"190","DOI":"10.25100\/cm.v45i4.1810","article-title":"Fragile X Syndrome S\u00edndrome de X Fr\u00e1gil","volume":"45","author":"Saldarriaga","year":"2014","journal-title":"Colomb. M\u00e9dica"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Randol, J.L., Kim, K., Ponzini, M.D., Tassone, F., Falcon, A.K., Hagerman, R.J., and Hagerman, P.J. (2024). Variation of FMRP Expression in Peripheral Blood Mononuclear Cells from Individuals with Fragile X Syndrome. Genes, 15.","DOI":"10.3390\/genes15030356"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1002\/mgg3.398","article-title":"Fragile X checklists: A meta-analysis and development of a simplified universal clinical checklist","volume":"6","author":"Lubala","year":"2018","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s12687-018-0374-4","article-title":"Usefulness of fragile X checklist and CGG distribution in specialized institutions in Kinshasa, DR Congo","volume":"10","author":"Lumaka","year":"2018","journal-title":"J. Community Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/0092-8674(93)90420-U","article-title":"The protein product of the fragile X gene, FMR1, has characteristics of an RNA-binding protein","volume":"74","author":"Siomi","year":"1993","journal-title":"Cell"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"S216","DOI":"10.1542\/peds.2016-1159H","article-title":"Fragile X Newborn Screening: Lessons Learned From a Multisite Screening Study","volume":"139","author":"Bailey","year":"2017","journal-title":"Pediatrics"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.jad.2015.07.046","article-title":"Self-reported stigma and symptoms of anxiety and depression in people with intel-lectual disabilities: Findings from a cross sectional study in England","volume":"187","author":"Ali","year":"2015","journal-title":"J. Affect Disord."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e1615","DOI":"10.1002\/mgg3.1615","article-title":"Negotiating political power and stigma around fragile X Syndrome in a rural village in Cameroon: A tale of a royal family and a community","volume":"9","author":"Kamga","year":"2021","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1542\/peds.2013-4301","article-title":"Fragile X Syndrome: A Review of Associated Medical Problems","volume":"134","author":"Kidd","year":"2014","journal-title":"Pediatrics"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1352\/1944-7558-115.6.461","article-title":"Seizures in fragile X syndrome: Characteristics and comorbid diagnoses","volume":"115","author":"Raspa","year":"2010","journal-title":"Am. J. Intellect. Dev. Disabil."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1542\/peds.2008-0317","article-title":"Advances in the Treatment of Fragile X Syndrome","volume":"123","author":"Hagerman","year":"2009","journal-title":"Pediatrics"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1097\/DBP.0000000000000334","article-title":"A randomized, double-blind, place-bo-controlled trial of low-dose sertraline in young children with fragile X syndrome","volume":"37","author":"Hess","year":"2016","journal-title":"J. Dev. Behav. Pediatr."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e00745","DOI":"10.1002\/mgg3.745","article-title":"Cognitive and behavioral improvement in adults with fragile X syndrome treated with metformin-two cases","volume":"7","author":"Protic","year":"2019","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e956","DOI":"10.1002\/mgg3.956","article-title":"Metformin treatment in young children with fragile X syndrome","volume":"7","author":"Biag","year":"2019","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s11689-022-09466-6","article-title":"A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX)","volume":"14","author":"Hagerman","year":"2022","journal-title":"J. Neurodev. Disord."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/s41591-021-01321-w","article-title":"Inhibition of phosphodiesterase-4D in adults with fragile X syndrome: A randomized, placebo-controlled, phase 2 clinical trial","volume":"27","author":"Harnett","year":"2021","journal-title":"Nat. Med."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/6\/683\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:48:40Z","timestamp":1760107720000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/6\/683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,25]]},"references-count":102,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["genes15060683"],"URL":"https:\/\/doi.org\/10.3390\/genes15060683","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,25]]}}}