dc.date.accessioned | 2019-02-05T13:54:47Z | |
dc.date.available | 2019-02-05T13:54:47Z | |
dc.date.created | 2018-07-24T13:48:16Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Kotlarz, Daniel Marquardt, Benjamin Barøy, Tuva Lee, Way S. Konnikova, Liza Hollizeck, Sebastian Magg, Thomas Lehle, Anna S. Walz, Christoph Borggraefe, Ingo Hauck, Fabian Bufler, Philip Conca, Raffaele Wall, Sarah M. Schumacher, Eva Margrethe Misceo, Doriana Frengen, Eirik Bentsen, Beint Sigmund Uhlig, Holm H. Hopfner, Karl-Peter Muise, Aleixo M. Snapper, Scott B. Strømme, Petter Klein, Christoph . Human TGF-β1 deficiency causes severe inflammatory bowel disease and encephalopathy. Nature Genetics. 2018, 50(3), 344-348 | |
dc.identifier.uri | http://hdl.handle.net/10852/66399 | |
dc.description.abstract | Transforming growth factor (TGF)-β1 (encoded by TGFB1) is the prototypic member of the TGF-β family of 33 proteins that orchestrate embryogenesis, development and tissue homeostasis1,2. Following its discovery3, enormous interest and numerous controversies have emerged about the role of TGF-β in coordinating the balance of pro- and anti-oncogenic properties4,5, pro- and anti-inflammatory effects6, or pro- and anti-fibrinogenic characteristics7. Here we describe three individuals from two pedigrees with biallelic loss-of-function mutations in the TGFB1 gene who presented with severe infantile inflammatory bowel disease (IBD) and central nervous system (CNS) disease associated with epilepsy, brain atrophy and posterior leukoencephalopathy. The proteins encoded by the mutated TGFB1 alleles were characterized by impaired secretion, function or stability of the TGF-β1–LAP complex, which is suggestive of perturbed bioavailability of TGF-β1. Our study shows that TGF-β1 has a critical and nonredundant role in the development and homeostasis of intestinal immunity and the CNS in humans. | en_US |
dc.language | EN | |
dc.title | Human TGF-β1 deficiency causes severe inflammatory bowel disease and encephalopathy | en_US |
dc.type | Journal article | en_US |
dc.creator.author | Kotlarz, Daniel | |
dc.creator.author | Marquardt, Benjamin | |
dc.creator.author | Barøy, Tuva | |
dc.creator.author | Lee, Way S. | |
dc.creator.author | Konnikova, Liza | |
dc.creator.author | Hollizeck, Sebastian | |
dc.creator.author | Magg, Thomas | |
dc.creator.author | Lehle, Anna S. | |
dc.creator.author | Walz, Christoph | |
dc.creator.author | Borggraefe, Ingo | |
dc.creator.author | Hauck, Fabian | |
dc.creator.author | Bufler, Philip | |
dc.creator.author | Conca, Raffaele | |
dc.creator.author | Wall, Sarah M. | |
dc.creator.author | Schumacher, Eva Margrethe | |
dc.creator.author | Misceo, Doriana | |
dc.creator.author | Frengen, Eirik | |
dc.creator.author | Bentsen, Beint Sigmund | |
dc.creator.author | Uhlig, Holm H. | |
dc.creator.author | Hopfner, Karl-Peter | |
dc.creator.author | Muise, Aleixo M. | |
dc.creator.author | Snapper, Scott B. | |
dc.creator.author | Strømme, Petter | |
dc.creator.author | Klein, Christoph | |
cristin.unitcode | 185,53,18,10 | |
cristin.unitname | Avdeling for medisinsk genetikk | |
cristin.ispublished | true | |
cristin.fulltext | postprint | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 1598501 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nature Genetics&rft.volume=50&rft.spage=344&rft.date=2018 | |
dc.identifier.jtitle | Nature Genetics | |
dc.identifier.volume | 50 | |
dc.identifier.issue | 3 | |
dc.identifier.startpage | 344 | |
dc.identifier.endpage | 348 | |
dc.identifier.doi | http://dx.doi.org/10.1038/s41588-018-0063-6 | |
dc.identifier.urn | URN:NBN:no-69617 | |
dc.type.document | Tidsskriftartikkel | en_US |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 1061-4036 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/66399/2/KotlarzNatGenetFinal.pdf | |
dc.type.version | AcceptedVersion | |