Long-read DNA and RNA Sequencing Reveal Treacher Collins Syndrome Cause

Strategic Insights -

Researchers at Erasmus University Medical Center have made a groundbreaking discovery in the field of genetics, pinpointing the cause of Treacher Collins syndrome, a rare craniofacial genetic disorder. The study, published in a recent issue of HGG Advances, reveals that a large genomic insertion in the TCOF1 gene, caused by a retrotransposon insertion, leads to the syndrome. This work demonstrates the potential of long-read DNA and RNA sequencing in identifying pathogenic variants in unexplained genetic disorders.

Key Takeaways:

  • Researchers at Erasmus University Medical Center identified the cause of Treacher Collins syndrome as a large genomic insertion in the TCOF1 gene, caused by a retrotransposon insertion.
  • Long-read DNA and RNA sequencing revealed the aberrant expression of TCOF1 and optical genome mapping detected a large genomic insertion in the TCOF1 gene.
  • The study demonstrated the potential of long-read sequencing in identifying pathogenic variants in unexplained genetic disorders.
  • The researchers identified mosaicism in the father of the two affected half-siblings, indicating a complex genetic scenario.
  • The study's findings highlight the importance of long-read sequencing in uncovering the genetic causes of rare genetic disorders.
  • The researchers also identified the involvement of several genes, including TCOF1, POLR1B, POLR1C, and POLR1D, in the development of the syndrome.

Statistics:

  • 3.5 kb SINE-VNTR-Alu (SVA) retrotransposon insertion in intron 17 of TCOF1 was detected.
  • Long-read RNA-seq demonstrated that the insertion was partially exonized, inducing an isoform switch to the shorter non-canonical TCOF1 isoform c.
  • 100% confirmation of SVA-insertion in both half-siblings.
  • 50% mosaicism in the father, indicating the presence of both affected and unaffected cells.

Sources:

  • Long-read DNA and RNA sequencing reveal an intronic retrotransposon insertion in TCOF1 causing Treacher Collins syndrome (HGG Advances, 2025:100523).
  • NewsRx. Study Data from Erasmus University Medical Center Update Knowledge of Treacher-Collins Syndrome (Long-read DNA and RNA sequencing reveal an intronic retrotransposon insertion in TCOF1 causing Treacher Collins syndrome) (Health & Medicine Week, October 17, 2025; p 7720).