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Background <p>Lynch syndrome is due to error in DNA mismatch repair (MMR) genes caused by germline pathogenic variants. For some families highly suspicious of Lynch syndrome, the diagnosis may not be confirmed.</p> Case presentation <p>We present a family where Lynch syndrome has been suspected for 20&#xa0;years. Although haplotyping and tumor analyses suggested Lynch syndrome, newer sequencing methods such as whole-genome sequencing and long-read sequencing, were needed to detect the underlying genetic cause of their cancer predisposition. We identified a &gt; 3kbp retrotransposon (RT) insertion in <i>MSH6</i> to be the causative germline variant. Further, we reviewed the literature for RT events in Lynch syndrome families and found a total of 40 RT cases, making up about 0.5% of Lynch cases. Two-third of the RTs were shorter ALU-elements (&lt; 500&#xa0;bp).</p> Conclusions <p>Although RTs insertions do not seem to be a common cause of Lynch syndrome, the number might be underestimated because of the difficulties in detecting these variants with well-established methods like Sanger sequencing and NGS target sequencing.</p>

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Lynch syndrome caused by SINE-VNTR-Alu-F retrotransposon insert in MSH6 confirmed after 20 years of testing: a case report and literature review

  • 期刊论文

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  • 发表日期：

    2025年10月14日

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  • Wenche Sjursen,
  • Eva Kathrine Svaasand,
  • Bodil Gilde,
  • Anuradha Ravi,
  • Katinka Madtzog Korseth,
  • Ashish Kumar Singh,
  • Jostein Johansen,
  • Olaug Kristin Rødningen,
  • Sofie Geck Sevatdal,
  • Siv Anita Hegre,
  • Maren Fridtjofsen Olsen,
  • Kristine Misund

摘要

Background

Lynch syndrome is due to error in DNA mismatch repair (MMR) genes caused by germline pathogenic variants. For some families highly suspicious of Lynch syndrome, the diagnosis may not be confirmed.

Case presentation

We present a family where Lynch syndrome has been suspected for 20 years. Although haplotyping and tumor analyses suggested Lynch syndrome, newer sequencing methods such as whole-genome sequencing and long-read sequencing, were needed to detect the underlying genetic cause of their cancer predisposition. We identified a > 3kbp retrotransposon (RT) insertion in MSH6 to be the causative germline variant. Further, we reviewed the literature for RT events in Lynch syndrome families and found a total of 40 RT cases, making up about 0.5% of Lynch cases. Two-third of the RTs were shorter ALU-elements (< 500 bp).

Conclusions

Although RTs insertions do not seem to be a common cause of Lynch syndrome, the number might be underestimated because of the difficulties in detecting these variants with well-established methods like Sanger sequencing and NGS target sequencing.