Comprehensive analysis of genomic complexity in the 5’ end coding region of the DMD gene in patients of exons 1–2 duplications based on long-read sequencing

• DOI: 10.1186/s12864-024-10224-2
• Publication Date: 2024-03-19T09:05:16Z
• Authors: Jiandong Shen; Taoli Ding; Xueping Sun; Ji Yang; Yue Zhang; Jing Wang; Mengdi Ge; Heng Xu; Jiazi Xie; Fei Wang; Feiyang Diao
• Keywords: Breakpoint

Abstract Background Dystrophinopathies are the most common X-linked inherited muscle diseases, and disease-causing gene is DMD . Exonic duplications a type of pathogenic variants in gene, however, 5’ end exonic containing exon 1 less common. When assessing pathogenicity consideration must be given to their impact on reading frame. Traditional molecular methods, such as multiplex ligation-dependent probe amplification (MLPA) next-generation sequencing (NGS), commonly used clinics. However, they cannot discriminate precise physical locations breakpoints structural features genomic rearrangement. Long-read (LRS) can effectively overcome this limitation. Results We LRS technology perform whole genome three families analyze variations which involves and/or 2. Two distinct variant types encompassing Dp427m isoform Dp427c identified, have been infrequently reported previously. In pedigree 1, male individuals harboring duplication consecutive exons 1–2 canonical transcript (Dp427m) normal, indicating likely benign. 3, patient carries complex SVs involving showing an obvious phenotype. The characteristics (SVs) identified by LRS, enabling classification variants' pathogenicity. Conclusions Our research sheds light complexity Dp427c/Dp427m promoter regions emphasizes importance cautious interpretation when 5' duplications, particularly carrier screening scenarios without affected proband.