Journal article
Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome
- Abstract:
- The gene IL6ST encodes GP130, the common signal transducer of the IL-6 cytokine family consisting of 10 cytokines. Previous studies have identified cytokine-selective IL6ST defects that preserve LIF signaling. We describe three unrelated families with at least five affected individuals who presented with lethal Stüve-Wiedemann-like syndrome characterized by skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. We identified essential loss-of-function variants in IL6ST (a homozygous nonsense variant and a homozygous intronic splice variant with exon skipping). Functional tests showed absent cellular responses to GP130-dependent cytokines including IL-6, IL-11, IL-27, oncostatin M (OSM), and leukemia inhibitory factor (LIF). Genetic reconstitution of GP130 by lentiviral transduction in patient-derived cells reversed the signaling defect. This study identifies a new genetic syndrome caused by the complete lack of signaling of a whole family of GP130-dependent cytokines in humans and highlights the importance of the LIF signaling pathway in pre- and perinatal development.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 4.4MB, Terms of use)
-
- Publisher copy:
- 10.1084/jem.20191306
Authors
- Publisher:
- Rockefeller University Press
- Journal:
- Journal of Experimental Medicine More from this journal
- Volume:
- 217
- Issue:
- 3
- Article number:
- e20191306
- Publication date:
- 2020-01-08
- Acceptance date:
- 2019-11-14
- DOI:
- EISSN:
-
1540-9538
- ISSN:
-
0022-1007
- Language:
-
English
- Pubs id:
-
pubs:1081478
- UUID:
-
uuid:2ea9a15c-6b74-4594-9612-16d12bf7a274
- Local pid:
-
pubs:1081478
- Source identifiers:
-
1081478
- Deposit date:
-
2020-01-10
Terms of use
- Copyright holder:
- Chen et al
- Copyright date:
- 2020
- Notes:
- © 2020 Chen et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
If you are the owner of this record, you can report an update to it here: Report update to this record