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

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title = "Absence of GP130 cytokine receptor signaling causes extended St{\"u}ve-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 St{\"u}ve-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.",
author = "Chen, {Yin Huai} and Giedre Grigelioniene and Newton, {Phillip T.} and Jacob Gullander and Maria Elfving and Anna Hammarsj{\"o} and Dominyka Batkovskyte and Alsaif, {Hessa S.} and Kurdi, {Wesam I.Y.} and Firdous Abdulwahab and Veerabahu Shanmugasundaram and Luke Devey and S{\'e}verine Bacrot and Jana Brodszki and Celine Huber and Ben Hamel and David Gisselsson and Nikos Papadogiannakis and Katarina Jedrycha and Barbara G{\"u}rtl-Lackner and Chagin, {Andrei S.} and Gen Nishimura and Dominik Aschenbrenner and Alkuraya, {Fowzan S.} and Arian Laurence and Val{\'e}rie Cormier-Daire and Uhlig, {Holm H.}",
year = "2020",
doi = "10.1084/jem.20191306",
language = "English",
volume = "217",
journal = "Journal of Experimental Medicine",
issn = "1540-9538",
publisher = "Rockefeller University Press",
number = "3",