{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T22:18:18Z","timestamp":1788387498782,"version":"build-2803163510"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations in the\n                      <jats:italic>DMD<\/jats:italic>\n                      gene. Understanding the carrier frequency and mutation spectrum in specific populations is critical for genetic counseling and early intervention. However, data on DMD carrier frequency among women of childbearing age and early pregnancy in Yueyang City, China, remain limited. This study aimed to characterize the carrier rate and mutation profile to support preventive strategies and reduce disease incidence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 25,611 women of childbearing age or early pregnancy from Yueyang City were enrolled. Combined next-generation sequencing and multiplex ligation-dependent probe amplification were used to detect pathogenic\/likely pathogenic (P\/LP) variants, copy number variants (CNVs), and small indels. Variants were classified per established guidelines. Carrier rates and geographical distribution were analyzed. Prenatal diagnosis was offered to identified carriers with follow-up to assess outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-eight women were identified as P\/LP carriers (0.11%), representing 25 distinct variants. CNVs constituted the majority (71.43%), with exon 45\u201355 deletions (64.29%) predominating over duplications (7.14%); notably, 13\/18 CNVs clustered in this hotspot. SNVs and small indels accounted for the remaining 28.57%. Intra-regional variation was marked, with the highest rate in Yunxi District (0.74%). Additionally, 81 VUSs (51 distinct types) were detected, 66.67% being missense. One male fetus inheriting a maternal VUS developed DMD-like features postpartum. Overall, 12 variants (1 LP, 11 VUSs) were previously unreported, including a nonsense variant c.3502G&amp;gt;T (p.E1168*) classified as LP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This first population-based study in Yueyang City, China, characterized the DMD carrier frequency (0.11%) and mutation spectrum among women of childbearing age or in early pregnancy. It revealed geographical heterogeneity and a high prevalence of CNVs, especially exon 45\u201355 deletions. Crucially, it highlights the underappreciated screening value of VUS. We recommend focused attention on VUS, particularly those with Bayesian scores \u22653, in genetic counseling and prenatal diagnosis to improve preventive strategies and reduce DMD incidence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1889156","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T22:10:30Z","timestamp":1788387030000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Spectrum and carrier frequency of DMD in Yueyang, China: a population-based analysis using NGS and MLPA"],"prefix":"10.3389","volume":"17","author":[{"given":"Qun","family":"Zhu","sequence":"first","affiliation":[{"name":"Key Laboratory of Birth Defects Prevention and Control of Yueyang City","place":["Yueyang, Hunan, China"]},{"name":"Department of Medical Genetics, Yueyang Maternal and Child Health Hospital","place":["Yueyang, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects Prevention and Control of Yueyang City","place":["Yueyang, Hunan, China"]},{"name":"Department of Medical Genetics, Yueyang Maternal and Child Health Hospital","place":["Yueyang, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyao","family":"Zu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects Prevention and Control of Yueyang City","place":["Yueyang, Hunan, China"]},{"name":"Department of Medical Genetics, Yueyang Maternal and Child Health Hospital","place":["Yueyang, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects Prevention and Control of Yueyang City","place":["Yueyang, Hunan, China"]},{"name":"Department of Medical Genetics, Yueyang Maternal and Child Health Hospital","place":["Yueyang, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liya","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects Prevention and Control of Yueyang City","place":["Yueyang, Hunan, China"]},{"name":"Department of Medical Genetics, Yueyang Maternal and Child Health Hospital","place":["Yueyang, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects Prevention and Control of Yueyang City","place":["Yueyang, Hunan, China"]},{"name":"Department of Medical Genetics, Yueyang Maternal and Child Health Hospital","place":["Yueyang, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Liu","sequence":"additional","affiliation":[{"name":"Technical Enablement Center, Zhejiang Biosan Bioscience Co., Ltd.","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Sun","sequence":"additional","affiliation":[{"name":"Technical Enablement Center, Zhejiang Biosan Bioscience Co., Ltd.","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuzhen","family":"Huang","sequence":"additional","affiliation":[{"name":"Technical Enablement Center, Zhejiang Biosan Bioscience Co., Ltd.","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobu","family":"Shen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects Prevention and Control of Yueyang City","place":["Yueyang, Hunan, China"]},{"name":"Department of Medical Genetics, Yueyang Maternal and Child Health Hospital","place":["Yueyang, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"46","DOI":"10.3390\/jpm11010046","article-title":"A genotype-phenotype correlation study of exon skip-equivalent In-Frame deletions and exon skip-amenable out-of-frame deletions across the DMD gene to simulate the effects of Exon-Skipping therapies: a meta-analysis","volume":"11","author":"Anwar","year":"2021","journal-title":"J. Pers. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"315","DOI":"10.3233\/JND-200555","article-title":"Parent project muscular dystrophy females with dystrophinopathy conference, Orlando, Florida June 26 - june 27, 2019","volume":"8","author":"Apkon","year":"2021","journal-title":"J. Neuromuscul. Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e1633","DOI":"10.1002\/mgg3.1633","article-title":"Matrilineal analysis of mutations in the DMD gene in a multigenerational south Indian cohort using DMD gene panel sequencing","volume":"9","author":"Arun","year":"2021","journal-title":"Mol. Genet. Genomic Med."},{"key":"B4","article-title":"Genetics, X-Linked inheritance","volume-title":"Statpearls","author":"Basta","year":"2023"},{"key":"B5","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.ajhg.2023.11.009","article-title":"ClinGen guidance for use of the PP1\/BS4 co-segregation and PP4 phenotype specificity criteria for sequence variant pathogenicity classification","volume":"111","author":"Biesecker","year":"2024","journal-title":"Am. J. Hum. Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e001977","DOI":"10.1136\/openhrt-2022-001977","article-title":"Cardiac care of children with dystrophinopathy and females carrying DMD-Gene variations","volume":"9","author":"Bourke","year":"2022","journal-title":"Open Heart"},{"key":"B7","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1007\/s00438-020-01757-8","article-title":"A female carrier of a novel DMD mutation with slightly skewed X-chromosome inactivation shows a suspected case of becker muscular dystrophy in a Chinese family","volume":"296","author":"Chen","year":"2021","journal-title":"Mol. Genet. Genomics"},{"key":"B8","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":"B9","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1002\/pd.6201","article-title":"Large scale population screening for duchenne muscular dystrophy-predictable and unpredictable challenges","volume":"42","author":"Cohen","year":"2022","journal-title":"Prenat. Diagn"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2593","DOI":"10.1053\/j.jvca.2021.09.047","article-title":"Orthotopic heart transplantation in manifesting carrier of Duchenne muscular dystrophy","volume":"36","author":"Cullom","year":"2022","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1016\/j.nmd.2021.08.004","article-title":"The DMD gene and therapeutic approaches to restore dystrophin","volume":"31","author":"Fortunato","year":"2021","journal-title":"Neuromuscul. Disord."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1038\/s41431-020-0643-7","article-title":"EMQN best practice guidelines for genetic testing in dystrophinopathies","volume":"28","author":"Fratter","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1360224","DOI":"10.3389\/fgene.2024.1360224","article-title":"The complex landscape of DMD mutations: moving towards personalized medicine","volume":"15","author":"Gatto","year":"2024","journal-title":"Front. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e1759","DOI":"10.1002\/mgg3.1759","article-title":"MLPA followed by target-NGS to detect mutations in the dystrophin gene of Peruvian patients suspected of DMD\/DMB","volume":"9","author":"Guevara-Fujita","year":"2021","journal-title":"Mol. Genet. Genomic Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"8396429","DOI":"10.1155\/2020\/8396429","article-title":"Population-Wide Duchenne Muscular Dystrophy carrier detection by CK and molecular testing","volume":"2020","author":"Han","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"B16","doi-asserted-by":"publisher","first-page":"100870","DOI":"10.1016\/j.gim.2023.100870","article-title":"Management of individuals with germline pathogenic\/likely pathogenic variants in CHEK2: a clinical practice resource of the American college of medical genetics and genomics (ACMG)","volume":"25","author":"Hanson","year":"2023","journal-title":"Genet. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1186\/s12920-023-01746-x","article-title":"Prenatal diagnosis of 1408 foetuses at risk of DMD\/BMD by MLPA and sanger sequencing combined with STR linkage analysis","volume":"16","author":"Hua","year":"2023","journal-title":"BMC Med. Genomics"},{"key":"B18","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s13023-022-02231-x","article-title":"Application of a next-generation sequencing (NGS) panel in newborn screening efficiently identifies inborn disorders of neonates","volume":"17","author":"Huang","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.cca.2022.11.024","article-title":"Newborn screening and genomic analysis of Duchenne muscular dystrophy in Henan, China","volume":"539","author":"Jia","year":"2023","journal-title":"Clin. Chim. Acta."},{"key":"B20","doi-asserted-by":"publisher","first-page":"53","DOI":"10.36185\/2532-1900-354","article-title":"Cognitive function in DMD carriers: personal case series and literature review","volume":"42","author":"Laura Carraro Arianna Iosca","year":"2023","journal-title":"Acta Myol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.nmd.2023.08.008","article-title":"Clinical, pathological, and genetic characterization in a large Chinese cohort with female dystrophinopathy","volume":"33","author":"Liu","year":"2023","journal-title":"Neuromuscul. Disord."},{"key":"B22","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.ijcard.2020.05.052","article-title":"Duchenne and becker muscular dystrophy carriers: evidence of cardiomyopathy by exercise and cardiac MRI testing","volume":"316","author":"Mah","year":"2020","journal-title":"Int. J. Cardiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"110614","DOI":"10.1016\/j.clinbiochem.2023.110614","article-title":"Factors influencing creatine kinase-MM concentrations in newborns and implications for newborn screening for Duchenne muscular dystrophy","volume":"118","author":"Maloney","year":"2023","journal-title":"Clin. Biochem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"100038","DOI":"10.1016\/j.gmg.2025.100038","article-title":"Unlocking the genetic blueprint of Duchenne muscular dystrophy: a personalized approach with MLPA and WES. Glob med genet","volume":"12","author":"Mathur","year":"2025","journal-title":"Glob. Med. Genet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"102583","DOI":"10.1016\/j.gim.2026.102583","article-title":"Points to consider for the reporting of variants of uncertain significance in germline genetic and genomic testing: a statement of the American college of medical genetics and genomics (ACMG)","volume":"12","author":"Mighton","year":"2026","journal-title":"Genet. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1146\/annurev-med-081117-010451","article-title":"CRISPR correction of Duchenne muscular dystrophy","volume":"70","author":"Min","year":"2019","journal-title":"Annu. Rev. Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1002\/humu.24191","article-title":"A single NGS-Based assay covering the entire genomic sequence of the DMD gene facilitates diagnostic and newborn screening confirmatory testing","volume":"42","author":"Nallamilli","year":"2021","journal-title":"Hum. Mutat."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e1892","DOI":"10.1002\/jgc4.1892","article-title":"Genetic counseling for the dystrophinopathies-practice resource of the national society of genetic counselors","volume":"34","author":"Pickart","year":"2025","journal-title":"J. Genet. Couns."},{"key":"B29","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1007\/s00415-025-12987-4","article-title":"Deep characterization of females with heterozygous Duchenne muscular dystrophy mutations","volume":"272","author":"Pietro","year":"2025","journal-title":"J. Neurol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"33","DOI":"10.36185\/2532-1900-1096","article-title":"Females with X-Linked muscle disorders: an underestimated patient population","volume":"44","author":"Politano","year":"2025","journal-title":"Acta Myol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"100947","DOI":"10.1016\/j.gim.2023.100947","article-title":"The landscape of reported VUS in multi-gene panel and genomic testing: time for a change","volume":"25","author":"Rehm","year":"2023","journal-title":"Genet. Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2230","DOI":"10.1038\/s41436-021-01150-9","article-title":"Correction: technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American college of medical genetics and genomics (ACMG) and the clinical genome resource (ClinGen)","volume":"23","author":"Riggs","year":"2021","journal-title":"Genet. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1007\/s10048-024-00788-2","article-title":"Dystrophinopathy patient data as a guide to interpretation of pregestational female population screening for DMD gene variants","volume":"26","author":"Sagi-Dain","year":"2024","journal-title":"Neurogenetics"},{"key":"B35","doi-asserted-by":"publisher","first-page":"111","DOI":"10.3390\/jpm10030111","article-title":"Advances in genetic characterization and genotype-phenotype correlation of duchenne and becker muscular dystrophy in the personalized medicine era","volume":"10","author":"Sheikh","year":"2020","journal-title":"J. Pers. Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1080\/13543784.2021.1868434","article-title":"Developing DMD therapeutics: a review of the effectiveness of small molecules, stop-codon readthrough, dystrophin gene replacement, and exon-skipping therapies","volume":"30","author":"Sheikh","year":"2021","journal-title":"Expert Opin. Investig. Drugs"},{"key":"B37","doi-asserted-by":"publisher","first-page":"100981","DOI":"10.1016\/j.gim.2023.100981","article-title":"Lessons learned from the first national population-based genetic carrier-screening program for Duchenne muscular dystrophy","volume":"25","author":"Singer","year":"2023","journal-title":"Genet. Med."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1097\/AOG.0000000000005318","article-title":"Reproductive carrier screening results with maternal health implications during pregnancy","volume":"142","author":"Souter","year":"2023","journal-title":"Obstet Gynecol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"837","DOI":"10.3390\/genes11080837","article-title":"Therapeutic strategies for Duchenne muscular dystrophy: an update","volume":"11","author":"Sun","year":"2020","journal-title":"Genes (Basel)"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1002\/acn3.51829","article-title":"Newborn screening for Duchenne muscular dystrophy: a two-year pilot study","volume":"10","author":"Tavakoli","year":"2023","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"3","DOI":"10.12703\/r\/12-3","article-title":"Vascular therapy for duchenne muscular dystrophy (DMD)","volume":"12","author":"Thapa","year":"2023","journal-title":"Fac. Rev."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e1932","DOI":"10.1002\/jgc4.1932","article-title":"A retrospective cohort study and review of the literature about germline mosaicism in duchenne\/becker muscular dystrophy prenatal counseling: how to estimate the recurrence risk in clinical settings?","volume":"34","author":"Verebi","year":"2025","journal-title":"J. Genet. Couns."},{"key":"B42","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.cca.2019.01.014","article-title":"Molecular genetic testing and diagnosis strategies for dystrophinopathies in the era of next generation sequencing","volume":"491","author":"Zhang","year":"2019","journal-title":"Clin. Chim. Acta"},{"key":"B43","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1038\/s10038-024-01263-4","article-title":"The recommendation of re-classification of variants of uncertain significance (VUS) in adult genetic disorders patients","volume":"69","author":"Zhang","year":"2024","journal-title":"J. Hum. Genet."},{"key":"B44","doi-asserted-by":"publisher","first-page":"3035","DOI":"10.3892\/mmr.2019.9982","article-title":"Clinical and genetic characteristics of female dystrophinopathy carriers","volume":"19","author":"Zhong","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"B45","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/s00246-020-02470-4","article-title":"Cardiac phenotype-genotype associations in DMD\/BMD: a meta-analysis and systematic review","volume":"42","author":"Zhou","year":"2021","journal-title":"Pediatr. Cardiol."},{"key":"B46","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.2026.1889156\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T22:10:32Z","timestamp":1788387032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1889156\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":47,"alternative-id":["10.3389\/fgene.2026.1889156"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2026.1889156","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"article-number":"1889156"}}