Scholarlink

Background <p>Duchenne muscular dystrophy (DMD) is an X-linked disorder caused by mutations in the <i>DMD</i> gene. Reports of DMD resulting from complex structural variants involving the <i>DMD</i> gene are rare, partly because such variants are often undetectable by standard diagnostic approaches such as multiplex ligation-dependent probe amplification (MLPA) and short-read whole-exome sequencing (WES).</p> Case presentation <p>Using long-read sequencing, we identified two unrelated pedigrees with complex structural rearrangements affecting the <i>DMD</i> locus. Case 1 carried an inversion encompassing exon 2 of <i>DMD</i>. Case 2 harbored a large-scale inversion of the <i>DMD</i> gene accompanied by two segmental duplications arising as a direct consequence of the inversion; the entire complex allele was maternally inherited. In both instances, simple tandem repeats were present at most of the breakpoints.</p> Conclusions <p>Our findings demonstrate that long-read sequencing is a powerful tool for resolving complex structural variants. The simple tandem repeats identified at the inversion breakpoints in DMD patients enhance our understanding of the mutational mechanisms underlying structural variation, which in turn aids in developing potential therapeutic strategies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Long-read sequencing identifies complex structural variants in DMD patients

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月29日

查看全文
  • Yi Xie,
  • Lijun Bao,
  • Xuenan Yu,
  • Yan Liu

摘要

Background

Duchenne muscular dystrophy (DMD) is an X-linked disorder caused by mutations in the DMD gene. Reports of DMD resulting from complex structural variants involving the DMD gene are rare, partly because such variants are often undetectable by standard diagnostic approaches such as multiplex ligation-dependent probe amplification (MLPA) and short-read whole-exome sequencing (WES).

Case presentation

Using long-read sequencing, we identified two unrelated pedigrees with complex structural rearrangements affecting the DMD locus. Case 1 carried an inversion encompassing exon 2 of DMD. Case 2 harbored a large-scale inversion of the DMD gene accompanied by two segmental duplications arising as a direct consequence of the inversion; the entire complex allele was maternally inherited. In both instances, simple tandem repeats were present at most of the breakpoints.

Conclusions

Our findings demonstrate that long-read sequencing is a powerful tool for resolving complex structural variants. The simple tandem repeats identified at the inversion breakpoints in DMD patients enhance our understanding of the mutational mechanisms underlying structural variation, which in turn aids in developing potential therapeutic strategies.