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@ARTICLE{Baumann:300248,
author = {A. A. Baumann and L. I. Knol and M. Arlt and T.
Hutschenreiter and A. Richter and T. J. Widmann and M.
Franke and K. Hackmann and S. Winkler and D. Richter$^*$ and
I. Spier and S. Aretz and D. Aust and J. Porrmann and D.
William and E. Schröck$^*$ and H. Glimm$^*$ and A. Jahn},
title = {{L}ong-read genome and {RNA} sequencing resolve a
pathogenic intronic germline {LINE}-1 insertion in {APC}.},
journal = {npj Genomic Medicine},
volume = {10},
number = {1},
issn = {2056-7944},
address = {London [u.a.]},
publisher = {Nature Publ. Group},
reportid = {DKFZ-2025-00709},
pages = {30},
year = {2025},
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.},
cin = {DD01},
ddc = {610},
cid = {I:(DE-He78)DD01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40180948},
doi = {DOI:10.1038/s41525-025-00485-5},
url = {https://inrepo02.dkfz.de/record/300248},
}