{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:30:54Z","timestamp":1787239854219,"version":"build-2736575974"},"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tertiary Education Trust Fund National Research Fund","award":["TETFund\/ES\/DR&D-CE\/NRF2024\/SETI\/HSW\/00032\/VOL.1"],"award-info":[{"award-number":["TETFund\/ES\/DR&D-CE\/NRF2024\/SETI\/HSW\/00032\/VOL.1"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>There is an increasing burden of neurodevelopmental disorders worldwide, with scarce data in low and middle-income countries, including Nigeria. Little is known about Fragile X disorders (Fragile X syndrome and Fragile X premutation-associated conditions) in developing countries and there is no national data in Nigeria. Advancing Mental Health and Well-being of Nigerian Children Through Public Health Screening for Fragile X Disorders (CHAMP-FX) is a multicentre public health screening initiative designed to estimate the prevalence of Fragile X disorders among children with neurodevelopmental disorders in Nigeria through targeted screening, strengthen diagnostic capacity and provide pathways to targeted treatments. This is a prospective multicentre screening study with longitudinal follow-up recruiting children aged 1\u201318 years with intellectual disability, autism spectrum disorder, and\/or global developmental delay from six tertiary hospitals across Nigeria\u2019s six geopolitical zones. Using purposive sampling, 102 participants (17 per zone) will be enrolled. Sociodemographic data and clinical evaluation will be obtained using KoboToolbox. Blood samples will be collected as dried spots on quick-response coded filter cards, stored with desiccant, and transported to the coordinating molecular laboratory. Genetic testing will be performed using a long-range amplification workflow followed by long-read sequencing to determine repeat sizes and classify results using internationally accepted thresholds. The primary outcome is the proportion of participants with Fragile X full mutation and\/or premutation in the selected cohort. Secondary outcomes include the distribution of repeat sizes and associations with sociodemographic and clinical variables. Screen-positive participants will receive structured result disclosure, genetic counselling, and referral for appropriate supportive interventions, with targeted therapy using metformin offered to participants diagnosed with Fragile X syndrome. Findings will be disseminated through peer-reviewed publication, conferences and stakeholder engagement.<\/jats:p>","DOI":"10.1371\/journal.pone.0355384","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T17:32:12Z","timestamp":1785951132000},"page":"e0355384","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Advancing mental health and well-being of Nigerian children through public health screening for Fragile X disorders (CHAMP-FX): protocol of a prospective multicentre screening study with longitudinal follow-up"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7030-5828","authenticated-orcid":true,"given":"Chioma Ngozichukwu Pauline","family":"Mbachu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin Ehi","family":"Eseigbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikechukwu Innocent","family":"Mbachu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George Uchenna","family":"Eleje","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0525-0888","authenticated-orcid":true,"given":"Ifeoma Bridget","family":"Udigwe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chika","family":"Onwuwamah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4197-1812","authenticated-orcid":true,"given":"Ifeoma Chisom","family":"Iloghalu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justus","family":"Onu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onochie Patrick","family":"Manafa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8396-0992","authenticated-orcid":true,"given":"Onyekachi","family":"Okonkwo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halima","family":"Adamu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasaki","family":"Aliu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chizalu Ifeyinwa","family":"Ndukwu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Ugochukwu","family":"Ndubuisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa Erezimena","family":"Ogholaja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1451-565X","authenticated-orcid":true,"given":"Samuel Okwuchukwu","family":"Ilikannu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahoma","family":"Mbanuzuru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2346-3345","authenticated-orcid":true,"given":"Kingsley","family":"Anukam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6634-8550","authenticated-orcid":true,"given":"Gbenga","family":"Olorunfemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2695-9370","authenticated-orcid":true,"given":"Amalachukwu Okwukweka","family":"Odita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divinefavour Malachy","family":"Echezona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uzoma","family":"Okereke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5863-7125","authenticated-orcid":true,"given":"Esther","family":"Umeadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald Okanandu","family":"Udigwe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7631-7362","authenticated-orcid":true,"given":"Amarachi Ujunwa","family":"Bayo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacinta","family":"Elo-Ilo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2796-6902","authenticated-orcid":true,"given":"Maria-Regina","family":"Idume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chijioke Elias","family":"Ezeudu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2664-0391","authenticated-orcid":true,"given":"Kelechi","family":"Odinaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zita Chidera","family":"Ezeno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binyelum","family":"Ofojebe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3621-2704","authenticated-orcid":true,"given":"Adaeze","family":"Obiegbu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chukwudubem","family":"Onyejiaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amara","family":"Egbogu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Obed Chukwuma","family":"Azubike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6636-5166","authenticated-orcid":true,"given":"Ngozi Chinenye","family":"Okeke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther Nwabuife","family":"Ugochukwu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1010-3022","authenticated-orcid":true,"given":"Sunday Onyemaechi","family":"Oriji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves-Ann Amaka","family":"Ezeuko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udoka Peace","family":"Adeniyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9904-9490","authenticated-orcid":true,"given":"Lazarus Ugochukwu","family":"Okafor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy Chinelo","family":"Ebenebe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwakwe","family":"Richard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8991-0091","authenticated-orcid":true,"given":"Clement Chukwudorue","family":"Ezechukwu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Tassone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randi","family":"Hagerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"pone.0355384.ref001","doi-asserted-by":"crossref","first-page":"121","DOI":"10.12688\/wellcomeopenres.13540.1","article-title":"Burden of neurodevelopmental disorders in low and middle-income countries: A systematic review and meta-analysis","volume":"2","author":"M Bitta","year":"2017","journal-title":"Wellcome Open Res"},{"key":"pone.0355384.ref002","unstructured":"Mbachu CNP, Schneider A, Santos E, Tassone F, Hagerman R. Fragile X-associated Tremor\/Ataxia Syndrome: A Rare Case with Unusually Extensive Neuropathy. Vol. 4, Extensive Neuropathy. Medp Neurol Neurosurg. 2024."},{"key":"pone.0355384.ref003","doi-asserted-by":"crossref","first-page":"17065","DOI":"10.1038\/nrdp.2017.65","article-title":"Fragile X syndrome","volume":"3","author":"RJ Hagerman","year":"2017","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"pone.0355384.ref004","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":"W Chonchaiya","year":"2009","journal-title":"Adv Pediatr"},{"key":"pone.0355384.ref005","doi-asserted-by":"crossref","unstructured":"Mbachu CNP, Mbachu II, Hagerman R. A Comprehensive Review of Fragile X Syndrome and Fragile X Premutation Associated Conditions in Africa. Vol. 15, Genes. Multidisciplinary Digital Publishing Institute (MDPI); 2024.","DOI":"10.20944\/preprints202404.1713.v1"},{"issue":"1","key":"pone.0355384.ref006","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/cge.14619","article-title":"Knowledge and perceptions about fragile X syndrome and fragile X-premutation-associated conditions among medical doctors in Nigeria","volume":"107","author":"CNP Mbachu","year":"2025","journal-title":"Clin Genet"},{"key":"pone.0355384.ref007","unstructured":"World Health Organization. Developmental Difficulties in Early Childhood: Prevention Early Identification Assessment and Intervention in Low- and Middle-Income Countries: a Review. 2012;120."},{"key":"pone.0355384.ref008","unstructured":"World Health Organization. New report highlights neglected health needs of children with developmental disabilities. 2023 https:\/\/www.who.int\/news\/item\/15-09-2023-new-reports-highlights-neglected-health-needs-of-children-with-developmental-disabilities"},{"key":"pone.0355384.ref009","unstructured":"World Bank. Nigeria | Data. World Bank Group. 202 https:\/\/data.worldbank.org\/country\/nigeria"},{"key":"pone.0355384.ref010","first-page":"247","article-title":"Part 1: Statistical Methods for Sample Size Determination","volume-title":"World Health Organization. Adequacy of Sample Size in Health Studies","author":"S Lemeshow","year":"1990"},{"key":"pone.0355384.ref011","doi-asserted-by":"crossref","first-page":"947","DOI":"10.2147\/NDT.S461650","article-title":"The Unmasking of Autism in South Africa and Nigeria","volume":"20","author":"SN Adams","year":"2024","journal-title":"Neuropsychiatr Dis Treat"},{"key":"pone.0355384.ref012","doi-asserted-by":"crossref","unstructured":"Hagerman RJ, Amiri K, Cronister A. Fragile X Checklist. Am J Med Genet. 1991;38:283\u20137.","DOI":"10.1002\/ajmg.1320380223"},{"issue":"6","key":"pone.0355384.ref013","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/0092-8674(91)90283-5","article-title":"Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradox","volume":"67","author":"YH Fu","year":"1991","journal-title":"Cell"},{"issue":"12","key":"pone.0355384.ref014","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/gm401","article-title":"FMR1 CGG allele size and prevalence ascertained through newborn screening in the United States","volume":"4","author":"F Tassone","year":"2012","journal-title":"Genome Med"},{"issue":"4","key":"pone.0355384.ref015","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":"I Fernandez-Carvajal","year":"2009","journal-title":"J Mol Diagn"},{"issue":"3","key":"pone.0355384.ref016","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/j.1399-0004.1997.tb02535.x","article-title":"Expand Long PCR for fragile X mutation detection","volume":"52","author":"S He\u0107imovi\u0107","year":"1997","journal-title":"Clin Genet"},{"issue":"3","key":"pone.0355384.ref017","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1373\/clinchem.2009.136101","article-title":"A novel FMR1 PCR method for the routine detection of low abundance expanded alleles and full mutations in fragile X syndrome","volume":"56","author":"S Filipovic-Sadic","year":"2010","journal-title":"Clin Chem"},{"issue":"1","key":"pone.0355384.ref018","first-page":"43","article-title":"A Rapid Polymerase Chain Reaction-Based Screening Method for Identification of All Expanded Alleles of the Fragile X (FMR1) Gene in Newborn and High-Risk Populations. J Mol Diagn","volume":"10","author":"F Tassone","year":"2008"},{"issue":"1","key":"pone.0355384.ref019","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":"F Tassone","year":"2000","journal-title":"Am J Hum Genet"},{"key":"pone.0355384.ref020","unstructured":"Ligation sequencing amplicons V14 (SQK-LSK114). https:\/\/nanoporetech.com\/document\/ligation-sequencing-amplicons-sqk-lsk114"},{"key":"pone.0355384.ref021","unstructured":"Data analysis | Oxford Nanopore Technologies. https:\/\/nanoporetech.com\/document\/data-analysis"},{"key":"pone.0355384.ref022","doi-asserted-by":"crossref","first-page":"115931","DOI":"10.1016\/j.ab.2025.115931","article-title":"Oxford Nanopore third generation sequencing for analysis of FMR1 5\u2019UTR CGG repeat expansions","volume":"706","author":"X Yang","year":"2025","journal-title":"Anal Biochem"},{"key":"pone.0355384.ref023","unstructured":"Giesselmann P. Genome Analysis Methods using Long Read Nanopore Sequencing. 2021 https:\/\/refubium.fu-berlin.de\/bitstream\/handle\/fub188\/32936\/dissertation.pdf?sequence=3&isAllowed=y"},{"key":"pone.0355384.ref024","unstructured":"Hunter JE, Berry-Kravis E, Hipp H, Todd PK. FMR1 Disorders. GeneReviews\u00ae. 2024 May 16 https:\/\/www.ncbi.nlm.nih.gov\/sites\/books\/NBK1384"},{"issue":"1","key":"pone.0355384.ref025","doi-asserted-by":"crossref","first-page":"23","DOI":"10.14710\/jbtr.v6i1.7321","article-title":"Fragile X Syndrome and Targeted Treatments","volume":"6","author":"N Tassanakijpanich","year":"2020","journal-title":"J Biomed Transl Res"},{"key":"pone.0355384.ref026","first-page":"83","article-title":"FXTAS: New Advances and Treatments In: Fragile X syndrome and Premutation Disorders New developments and treatments","author":"V Martinez-Cerdeno","year":"2020"},{"issue":"20","key":"pone.0355384.ref027","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"Declaration of Helsinki: ethical principles for medical research involving human subjects","volume":"310","author":"World Medical Association","year":"2013","journal-title":"JAMA"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355384","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T17:32:17Z","timestamp":1785951137000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355384"}},"subtitle":[],"editor":[{"given":"David Chibuike","family":"Ikwuka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":27,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0355384","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]}}}