{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T18:50:11Z","timestamp":1763837411518,"version":"build-2065373602"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Duchenne muscular dystrophy (DMD) is a severe X-linked disorder caused by mutations in the <jats:italic>DMD<\/jats:italic> gene, and it has a global prevalence of 3.6 per 100,000 people. Despite its well-documented genetic basis, no previous studies have characterized DMD in Guatemala. We analyzed 33 genetically confirmed cases to estimate the prevalence, describe the mutation spectrum, and assess the clinical features. The prevalence was 0.61 per 100,000 men younger than 30 years. Symptoms began before the age of 5 years in 85% of cases, yet 60% cases were diagnosed after the age of 6 years, highlighting significant diagnostic delays. Deletions were the most common mutation (55%), followed by point mutations (30%) and duplications (15%), with two novel variants being identified. Most deletions clustered in the exon 45\u201355 hotspot. Nearly half of the cases were eligible for exon-skipping therapies. These findings reveal genetic heterogeneity in the Guatemalan population, substantial delays in diagnosis, and the need for improved access to genetic testing, targeted treatments, and a national DMD registry.<\/jats:p>","DOI":"10.3389\/fgene.2025.1595423","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T08:11:31Z","timestamp":1760688691000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic and clinical landscape of Duchenne muscular dystrophy in Guatemala: insights from a national study"],"prefix":"10.3389","volume":"16","author":[{"given":"M.","family":"Orozco","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Kestler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Ramirez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Cabrera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"De la Vega","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Al Khleifat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e00510","DOI":"10.1002\/mgg3.510","article-title":"DMD Open-access variant explorer (DOVE): a scalable, open-access, web-based tool to aid in clinical interpretation of genetic variants in the DMD gene","volume":"7","author":"Bailey","year":"2019","journal-title":"Mol Genet & Genomic med"},{"key":"B36","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/j.rmclc.2018.07.006","article-title":"New molecular biology diagnostic tools in neuromuscular diseases","volume":"29","author":"Bidinost","year":"2018","journal-title":"Rev. M\u00e9d Clin. Las Condes"},{"key":"B3","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1002\/humu.22758","article-title":"The TREAT-NMD DMD global database: analysis of more than 7,000 Duchenne muscular dystrophy mutations","volume":"36","author":"Bladen","year":"2015","journal-title":"Hum. Mutat."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.3390\/brainsci13111521","article-title":"Higher prevalence of nonsense pathogenic DMD variants in a single-center cohort from Brazil: a genetic profile study that may guide the choice of disease-modifying treatments","volume":"13","author":"Braga","year":"2023","journal-title":"Brain Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"4563","DOI":"10.1007\/s10072-022-06128-2","article-title":"Duchenne muscular dystrophy newborn screening: the first 50,000 newborns screened in Taiwan","volume":"43","author":"Chien","year":"2022","journal-title":"Neurol. Sci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1186\/s12859-018-2334-8","article-title":"A new cross-platform architecture for epi-info software suite","volume":"19","author":"Camp","year":"2018","journal-title":"BMC Bioinform.,"},{"key":"B34","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1016\/j.rmclc.2018.09.003","article-title":"Enfermedades neuromusculares. Epidemiolog\u00eda y pol\u00edtica de salud en Chile","volume":"29","author":"Castiglioni","year":"2018","journal-title":"Rev. Med. Clin. Condes."},{"key":"B6","volume-title":"Analysis of MLPA data using novel software coffalyser. NET by MRC-Holland. En: Badr eldin A. Modern approaches to quality control","author":"Coffa","year":"2011"},{"key":"B8","doi-asserted-by":"publisher","first-page":"148","DOI":"10.12688\/f1000research.73476.3","article-title":"Mutation spectrum analysis of DMD gene in Indonesian duchenne and becker muscular dystrophy patients","volume":"11","author":"Dwianingsih","year":"2023","journal-title":"F1000Rsearch"},{"key":"B9","doi-asserted-by":"publisher","first-page":"820","DOI":"10.3390\/jcm10040820","article-title":"Innovative therapeutic approaches for Duchenne muscular dystrophy","volume":"10","author":"Fortunato","year":"2021","journal-title":"J. Clin. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"992546","DOI":"10.3389\/fnins.2022.992546","article-title":"Clinical and genetic characteristics of Chinese duchenne\/becker muscular dystrophy patients with small mutations","volume":"16","author":"Gan","year":"2022","journal-title":"Front. Neurosci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1002\/cphy.c140048","article-title":"The dystrophin complex: structure, function, and implications for therapy","volume":"5","author":"Gao","year":"2015","journal-title":"Compr. Physiol."},{"key":"B13","volume-title":"Estimaciones y proyecciones de la poblaci\u00f3n total seg\u00fan sexo y edad. Revisi\u00f3n","year":"2019"},{"key":"B14","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1007\/s13311-022-01197-9","article-title":"CRISPR-Cas9 gene therapy for Duchenne muscular dystrophy","volume":"19","author":"Happi","year":"2022","journal-title":"Neurotherapeutics"},{"key":"B15","doi-asserted-by":"publisher","first-page":"475","DOI":"10.17843\/rpmesp.2019.363.4085","article-title":"Detecci\u00f3n de mutaciones causantes de distrofia muscular de Duchenne\/Becker: reacci\u00f3n en cadena de la polimerasa Multiplex vs. Amplificaci\u00f3n m\u00faltiple dependiente de ligaci\u00f3n por sondas","volume":"36","author":"Huam\u00e1n-Dianderas","year":"2019","journal-title":"Rev. Peru. Med. Exp. Salud P\u00fablica"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1212\/01.CON.0000440658.03557.f1","article-title":"Congenital muscular dystrophies and congenital myopathies","volume":"19","author":"Iannaccone","year":"2013","journal-title":"Continuum"},{"key":"B17","doi-asserted-by":"publisher","first-page":"248","DOI":"10.3988\/jcn.2015.11.3.248","article-title":"Clinical and genetic characterization of female dystrophinopathy","volume":"11","author":"Lee","year":"2015","journal-title":"J. Clin. Neurol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.braindev.2015.05.014","article-title":"Contributions of Japanese patients to development of antisense therapy for DMD","volume":"38","author":"Matsuo","year":"2016","journal-title":"Brain Dev.,"},{"key":"B19","doi-asserted-by":"publisher","first-page":"139","DOI":"10.2217\/cer-2021-0196","article-title":"Ataluren delays loss of ambulation and respiratory decline in nonsense mutation Duchenne muscular dystrophy patients","volume":"11","author":"McDonald","year":"2022","journal-title":"J. Comp. Eff. Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.pediatrneurol.2024.01.003","article-title":"Practical considerations for delandistrogene moxeparvovec gene therapy in patients with Duchenne muscular dystrophy","volume":"153","author":"Mendell","year":"2024","journal-title":"Pediatr. Neurol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"3896","DOI":"10.1007\/s00415-023-11687-1","article-title":"Safety and effectiveness of ataluren in patients with nonsense mutation DMD in the STRIDE registry compared with the CINRG duchenne natural history study (2015-2022): 2022 interim analysis","volume":"270","author":"Mercuri","year":"2023","journal-title":"J. Neu"},{"key":"B22","volume-title":"ClinVar: a public resource for genomic variation and phenotype","year":"2025"},{"key":"B24","doi-asserted-by":"publisher","first-page":"175675","DOI":"10.1016\/j.ejphar.2023.175675","article-title":"Duchenne muscular dystrophy: current treatment and emerging exon skipping and gene therapy approach","volume":"947","author":"Patterson","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s13023-017-0631-3","article-title":"The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review","volume":"12","author":"Ryder","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/s13018-022-02996-8","article-title":"Global prevalence of duchenne and becker muscular dystrophy: a systematic review and meta-analysis","volume":"17","author":"Salari","year":"2022","journal-title":"J Orthop Surg Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1186\/s13023-014-0210-9","article-title":"Comparative cost of illness analysis and assessment of health care burden of duchenne and becker muscular dystrophies in Germany","volume":"9","author":"Schreiber-Katz","year":"2014","journal-title":"Orphanet J. Rare Dis."},{"key":"B29","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1097\/WCO.0000000000001191","article-title":"An update on becker muscular dystrophy","volume":"36","author":"Straub","year":"2023","journal-title":"Curr. Opin. Neurol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"S343","DOI":"10.3233\/JND-210682","article-title":"Exon-skipping in Duchenne muscular dystrophy","volume":"8","author":"Takeda","year":"2021","journal-title":"J. Nneuromus Dis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e0237803","DOI":"10.1371\/journal.pone.0237803","article-title":"The position of nonsense mutations can predict the phenotype severity: a survey on the DMD gene","volume":"15","author":"Torella","year":"2020","journal-title":"PloS One"},{"key":"B32","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s13353-020-00605-0","article-title":"Small mutations in duchenne\/becker muscular dystrophy in 164 unrelated Polish patients","volume":"62","author":"Zimowski","year":"2021","journal-title":"J. Appl. Genet."},{"key":"B33","doi-asserted-by":"publisher","first-page":"12710","DOI":"10.3390\/ijms232112710","article-title":"Specificities of the DMD gene mutation spectrum in Russian patients","volume":"23","author":"Zinina","year":"2022","journal-title":"Int. J. Mol. Sci."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2025.1595423\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T08:11:33Z","timestamp":1760688693000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2025.1595423\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,17]]},"references-count":31,"alternative-id":["10.3389\/fgene.2025.1595423"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2025.1595423","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,17]]},"article-number":"1595423"}}