X;7 Translocation at p21.1 and q31.31 Disrupting DMD : A Multiomics Study of a Male Dystrophinopathy Case

Background Dystrophinopathy comprises a group of X‐linked recessive muscular disorders that primarily affect skeletal and/or cardiac muscles. Although more than 90% of dystrophinopathy patients exhibit detectable variants in the DMD gene, a small proportion of cases remain undiagnosed at the molecular level. Methods We employed an integrated multiomics approach, including RNA sequencing (RNA‐seq) of muscle tissue, optical genome mapping (OGM), short‐ and long‐read whole‐genome sequencing (WGS), and karyotype analysis to elucidate the genetic mechanism in a dystrophinopathy family. Results Integrated genomic analyses identified a balanced reciprocal translocation between Xp21.1 and 7q31.31 in the proband, with the X‐chromosomal breakpoint disrupting intron 20 of DMD . RNA sequencing of muscle tissue revealed severely reduced DMD transcript coverage downstream of the breakpoint, consistent with transcriptional interruption. Muscle immunohistochemistry showed absent dystrophin staining at the N‐terminus, rod domain, and C‐terminus, confirming loss of protein expression. The translocation was maternally inherited; the mother is a carrier with a dystrophinopathy phenotype. Conclusions We report the first male case of dystrophinopathy caused by an X;autosome translocation disrupting DMD , thereby expanding the mutational spectrum of this disorder. Our findings underscore the value of comprehensive genomic profiling in resolving diagnostically elusive dystrophinopathy cases.