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Background <p>Duchenne muscular dystrophy (DMD) is a severe disorder that primarily affects males due to its X-linked recessive inheritance. It is caused by pathogenic variants of the <i>DMD</i> gene, most commonly exonic deletions, duplications, or point mutations. Current routine genetic testing methods, including next-generation sequencing and multiplex ligation-dependent probe amplification, can identify pathogenic <i>DMD</i> variants in over 90% of clinically diagnosed patients. However, in rare cases, a molecular diagnosis cannot be established using routine methods.</p> Case presentation <p>We describe a follow-up genetic analysis, based on karyotyping and optical genome mapping (OGM), of a patient with clinically diagnosed DMD who initially had negative results in extensive routine genetic testing. Karyotyping revealed a paracentric X-chromosomal inversion with estimated breakpoints at p22.31 and p21.2. OGM fine-mapped this alteration as inv(X)(p22.2p21.1) and confirmed its pathogenicity by identifying the proximal breakpoint within intron 41 of <i>DMD</i>, thereby disrupting the gene and providing a definitive molecular genetic diagnosis.</p> Conclusions <p>Current results further underscore the important role of chromosomal inversions as causal in a subset of DMD patients who remain without a molecular diagnosis after routine testing. It also demonstrates the utility of OGM in providing detailed, gene-level insights into cytogenetic abnormalities observed in the diagnostics of neuromuscular disorders.</p>

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Optical genome mapping identifies a balanced inversion disrupting DMD in a patient with Duchenne muscular dystrophy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月7日

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  • Tuuni Turtinen,
  • Pirjo Isohanni,
  • Anna-Kaisa Anttonen,
  • Leena Huhti,
  • Katri Pylkäs,
  • Marketta Tikkanen,
  • Anna H. Hakonen,
  • Sonja Strang-Karlsson,
  • Tuomo Mantere

摘要

Background

Duchenne muscular dystrophy (DMD) is a severe disorder that primarily affects males due to its X-linked recessive inheritance. It is caused by pathogenic variants of the DMD gene, most commonly exonic deletions, duplications, or point mutations. Current routine genetic testing methods, including next-generation sequencing and multiplex ligation-dependent probe amplification, can identify pathogenic DMD variants in over 90% of clinically diagnosed patients. However, in rare cases, a molecular diagnosis cannot be established using routine methods.

Case presentation

We describe a follow-up genetic analysis, based on karyotyping and optical genome mapping (OGM), of a patient with clinically diagnosed DMD who initially had negative results in extensive routine genetic testing. Karyotyping revealed a paracentric X-chromosomal inversion with estimated breakpoints at p22.31 and p21.2. OGM fine-mapped this alteration as inv(X)(p22.2p21.1) and confirmed its pathogenicity by identifying the proximal breakpoint within intron 41 of DMD, thereby disrupting the gene and providing a definitive molecular genetic diagnosis.

Conclusions

Current results further underscore the important role of chromosomal inversions as causal in a subset of DMD patients who remain without a molecular diagnosis after routine testing. It also demonstrates the utility of OGM in providing detailed, gene-level insights into cytogenetic abnormalities observed in the diagnostics of neuromuscular disorders.