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Exonic duplications are a common type of pathogenic variants in the\n                      <jats:italic>DMD<\/jats:italic>\n                      gene, however, 5\u2019 end exonic duplications containing exon 1 are less common. When assessing the pathogenicity of exonic duplications in the\n                      <jats:italic>DMD<\/jats:italic>\n                      gene, consideration must be given to their impact on the reading frame. Traditional molecular methods, such as multiplex ligation-dependent probe amplification (MLPA) and next-generation sequencing (NGS), are commonly used in clinics. However, they cannot discriminate the precise physical locations of breakpoints and structural features of genomic rearrangement. Long-read sequencing (LRS) can effectively overcome this limitation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We used LRS technology to perform whole genome sequencing on three families and analyze the structural variations of the\n                      <jats:italic>DMD<\/jats:italic>\n                      gene, which involves the duplications of exon 1 and\/or exon 2. Two distinct variant types encompassing exon 1 in the\n                      <jats:italic>DMD<\/jats:italic>\n                      Dp427m isoform and\/or Dp427c isoform are identified, which have been infrequently reported previously. In pedigree 1, the male individuals harboring duplication variant of consecutive exons 1\u20132 in the\n                      <jats:italic>DMD<\/jats:italic>\n                      canonical transcript (Dp427m) and exon 1 in the Dp427c transcript are normal, indicating the variant is likely benign. In pedigree 3, the patient carries complex SVs involving exon 1 of the\n                      <jats:italic>DMD<\/jats:italic>\n                      Dp427c transcript showing an obvious phenotype. The locations of the breakpoints and the characteristics of structural variants (SVs) are identified by LRS, enabling the classification of the variants' pathogenicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our research sheds light on the complexity of\n                      <jats:italic>DMD<\/jats:italic>\n                      variants encompassing Dp427c\/Dp427m promoter regions and emphasizes the importance of cautious interpretation when assessing the pathogenicity of\n                      <jats:italic>DMD<\/jats:italic>\n                      5' end exonic duplications, particularly in carrier screening scenarios without an affected proband.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12864-024-10224-2","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T05:05:16Z","timestamp":1710824716000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Comprehensive analysis of genomic complexity in the 5\u2019 end coding region of the DMD gene in patients of exons 1\u20132 duplications based on long-read sequencing"],"prefix":"10.1186","volume":"25","author":[{"given":"Jiandong","family":"Shen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taoli","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueping","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdi","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiazi","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyang","family":"Diao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,19]]},"reference":[{"key":"10224_CR1","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1038\/s41431-020-0643-7","volume":"28","author":"C Fratter","year":"2020","unstructured":"Fratter C, Dalgleish R, Allen SK, Santos R, Abbs S, Tuffery-Giraud S, et al. 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This study was approved by the Institutional Review Board of the First Affiliated Hospital of Nanjing Medical University (No. 2023-SR-454).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"292"}}