Evidence map›Paper›PMID 40180948›Full record

ArticleNPJ genomic medicine2025

Long-read genome and RNA sequencing resolve a pathogenic intronic germline LINE-1 insertion in APC.

Alexandra A Baumann, Lisanne I Knol, Marie Arlt, Tim Hutschenreiter, Anja Richter, Thomas J Widmann, Marcus Franke, Karl Hackmann, Sylke Winkler, Daniela Richter and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ genomic medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Alexandra A Baumann *Institute for Clinical Genetics, University Hospital Carl Gustav Carus at TUD Dresden University of Technology and Faculty of Medicine of TUD Dresden University of Technology, Dresden, Germany.ORCID http://orcid.org/0009-0003-8946-8741
Lisanne I Knol *National Center for Tumor Diseases (NCT), NCT/UCC Dresden,, a partnership between DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, and Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.ORCID http://orcid.org/0000-0002-8975-0398
Marie ArltInstitute for Clinical Genetics, University Hospital Carl Gustav Carus at TUD Dresden University of Technology and Faculty of Medicine of TUD Dresden University of Technology, Dresden, Germany.
Tim HutschenreiterInstitute for Clinical Genetics, University Hospital Carl Gustav Carus at TUD Dresden University of Technology and Faculty of Medicine of TUD Dresden University of Technology, Dresden, Germany.ORCID http://orcid.org/0009-0007-6456-2108
Anja RichterInstitute for Clinical Genetics, University Hospital Carl Gustav Carus at TUD Dresden University of Technology and Faculty of Medicine of TUD Dresden University of Technology, Dresden, Germany.ORCID http://orcid.org/0009-0006-8923-5376
Thomas J WidmannNational Center for Tumor Diseases (NCT), NCT/UCC Dresden,, a partnership between DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, and Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.ORCID http://orcid.org/0000-0003-0544-7269
Marcus FrankeInstitute for Clinical Genetics, University Hospital Carl Gustav Carus at TUD Dresden University of Technology and Faculty of Medicine of TUD Dresden University of Technology, Dresden, Germany.ORCID http://orcid.org/0009-0008-6007-6513
Karl HackmannInstitute for Clinical Genetics, University Hospital Carl Gustav Carus at TUD Dresden University of Technology and Faculty of Medicine of TUD Dresden University of Technology, Dresden, Germany.ORCID http://orcid.org/0000-0003-4181-2120
Sylke WinklerMax Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.ORCID http://orcid.org/0000-0002-0915-3316
Daniela RichterNational Center for Tumor Diseases (NCT), NCT/UCC Dresden,, a partnership between DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, and Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.
Isabel SpierInstitute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0003-2407-7427
Stefan AretzInstitute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0002-5228-1890
Daniela AustInstitute of Pathology, University Hospital Carl Gustav Carus at TUD Dresden University, Dresden, Germany.ORCID http://orcid.org/0000-0002-4867-8852
Joseph PorrmannInstitute for Clinical Genetics, University Hospital Carl Gustav Carus at TUD Dresden University of Technology and Faculty of Medicine of TUD Dresden University of Technology, Dresden, Germany.ORCID http://orcid.org/0000-0001-8474-6309
Doreen WilliamInstitute for Clinical Genetics, University Hospital Carl Gustav Carus at TUD Dresden University of Technology and Faculty of Medicine of TUD Dresden University of Technology, Dresden, Germany.ORCID http://orcid.org/0000-0001-7824-5073
Evelin SchröckInstitute for Clinical Genetics, University Hospital Carl Gustav Carus at TUD Dresden University of Technology and Faculty of Medicine of TUD Dresden University of Technology, Dresden, Germany.ORCID http://orcid.org/0000-0002-3377-1704
Hanno GlimmNational Center for Tumor Diseases (NCT), NCT/UCC Dresden,, a partnership between DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, and Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.ORCID http://orcid.org/0000-0003-4104-1135
Arne JahnInstitute for Clinical Genetics, University Hospital Carl Gustav Carus at TUD Dresden University of Technology and Faculty of Medicine of TUD Dresden University of Technology, Dresden, Germany. Arne.Jahn@ukdd.de.ORCID http://orcid.org/0000-0003-1045-1908

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Familial adenomatous polyposis (FAP) is caused by pathogenic germline variants in the tumor suppressor gene APC. Confirmation of diagnosis was not achieved by cancer gene panel and exome sequencing or custom array-CGH in a family with suspected FAP across five generations. Long-read genome sequencing (PacBio), short-read genome sequencing (Illumina), short-read RNA sequencing, and further validations were performed in different tissues of multiple family members. Long-read genome sequencing resolved a 6 kb full-length intronic insertion of a heterozygous LINE-1 element between exons 7 and 8 of APC that could be detected but not fully resolved by short-read genome sequencing. Targeted RNA analysis revealed aberrant splicing resulting in the formation of a pseudo-exon with a premature stop codon. The variant segregated with the phenotype in several family members allowing its evaluation as likely pathogenic. This study supports the utility of long-read DNA sequencing and complementary RNA approaches to tackle unsolved cases of hereditary disease.

Identifiers

PMID40180948
PMCPMC11968988

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