Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome

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Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome. / Chen, Yin Huai; Grigelioniene, Giedre; Newton, Phillip T.; Gullander, Jacob; Elfving, Maria; Hammarsjö, Anna; Batkovskyte, Dominyka; Alsaif, Hessa S.; Kurdi, Wesam I.Y.; Abdulwahab, Firdous; Shanmugasundaram, Veerabahu; Devey, Luke; Bacrot, Séverine; Brodszki, Jana; Huber, Celine; Hamel, Ben; Gisselsson, David; Papadogiannakis, Nikos; Jedrycha, Katarina; Gürtl-Lackner, Barbara; Chagin, Andrei S.; Nishimura, Gen; Aschenbrenner, Dominik; Alkuraya, Fowzan S.; Laurence, Arian; Cormier-Daire, Valérie; Uhlig, Holm H.

I: The Journal of experimental medicine, Vol. 217, Nr. 3, e20191306, 2020.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Chen, YH, Grigelioniene, G, Newton, PT, Gullander, J, Elfving, M, Hammarsjö, A, Batkovskyte, D, Alsaif, HS, Kurdi, WIY, Abdulwahab, F, Shanmugasundaram, V, Devey, L, Bacrot, S, Brodszki, J, Huber, C, Hamel, B, Gisselsson, D, Papadogiannakis, N, Jedrycha, K, Gürtl-Lackner, B, Chagin, AS, Nishimura, G, Aschenbrenner, D, Alkuraya, FS, Laurence, A, Cormier-Daire, V & Uhlig, HH 2020, 'Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome', The Journal of experimental medicine, vol. 217, nr. 3, e20191306. https://doi.org/10.1084/jem.20191306

APA

Chen, Y. H., Grigelioniene, G., Newton, P. T., Gullander, J., Elfving, M., Hammarsjö, A., Batkovskyte, D., Alsaif, H. S., Kurdi, W. I. Y., Abdulwahab, F., Shanmugasundaram, V., Devey, L., Bacrot, S., Brodszki, J., Huber, C., Hamel, B., Gisselsson, D., Papadogiannakis, N., Jedrycha, K., ... Uhlig, H. H. (2020). Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome. The Journal of experimental medicine, 217(3), [e20191306]. https://doi.org/10.1084/jem.20191306

CBE

Chen YH, Grigelioniene G, Newton PT, Gullander J, Elfving M, Hammarsjö A, Batkovskyte D, Alsaif HS, Kurdi WIY, Abdulwahab F, Shanmugasundaram V, Devey L, Bacrot S, Brodszki J, Huber C, Hamel B, Gisselsson D, Papadogiannakis N, Jedrycha K, Gürtl-Lackner B, Chagin AS, Nishimura G, Aschenbrenner D, Alkuraya FS, Laurence A, Cormier-Daire V, Uhlig HH. 2020. Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome. The Journal of experimental medicine. 217(3):Article e20191306. https://doi.org/10.1084/jem.20191306

MLA

Vancouver

Author

Chen, Yin Huai ; Grigelioniene, Giedre ; Newton, Phillip T. ; Gullander, Jacob ; Elfving, Maria ; Hammarsjö, Anna ; Batkovskyte, Dominyka ; Alsaif, Hessa S. ; Kurdi, Wesam I.Y. ; Abdulwahab, Firdous ; Shanmugasundaram, Veerabahu ; Devey, Luke ; Bacrot, Séverine ; Brodszki, Jana ; Huber, Celine ; Hamel, Ben ; Gisselsson, David ; Papadogiannakis, Nikos ; Jedrycha, Katarina ; Gürtl-Lackner, Barbara ; Chagin, Andrei S. ; Nishimura, Gen ; Aschenbrenner, Dominik ; Alkuraya, Fowzan S. ; Laurence, Arian ; Cormier-Daire, Valérie ; Uhlig, Holm H. / Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome. I: The Journal of experimental medicine. 2020 ; Vol. 217, Nr. 3.

RIS

TY - JOUR

T1 - Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome

AU - Chen, Yin Huai

AU - Grigelioniene, Giedre

AU - Newton, Phillip T.

AU - Gullander, Jacob

AU - Elfving, Maria

AU - Hammarsjö, Anna

AU - Batkovskyte, Dominyka

AU - Alsaif, Hessa S.

AU - Kurdi, Wesam I.Y.

AU - Abdulwahab, Firdous

AU - Shanmugasundaram, Veerabahu

AU - Devey, Luke

AU - Bacrot, Séverine

AU - Brodszki, Jana

AU - Huber, Celine

AU - Hamel, Ben

AU - Gisselsson, David

AU - Papadogiannakis, Nikos

AU - Jedrycha, Katarina

AU - Gürtl-Lackner, Barbara

AU - Chagin, Andrei S.

AU - Nishimura, Gen

AU - Aschenbrenner, Dominik

AU - Alkuraya, Fowzan S.

AU - Laurence, Arian

AU - Cormier-Daire, Valérie

AU - Uhlig, Holm H.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85077754381&partnerID=8YFLogxK

U2 - 10.1084/jem.20191306

DO - 10.1084/jem.20191306

M3 - Article

C2 - 31914175

VL - 217

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 1540-9538

IS - 3

M1 - e20191306

ER -