Authors
Charlotte Gehin, Museer A Lone, Winston Lee, Laura Capolupo, Sylvia Ho, Adekemi M Adeyemi, Erica H Gerkes, Alexander PA Stegmann, Estrella López-Martín, Eva Bermejo-Sánchez, Beatriz Martínez-Delgado, Christiane Zweier, Cornelia Kraus, Bernt Popp, Vincent Strehlow, Daniel Gräfe, Ina Knerr, Eppie R Jones, Stefano Zamuner, Luciano A Abriata, Vidya Kunnathully, Brandon E Moeller, Anthony Vocat, Samuel Rommelaere, Jean-Philippe Bocquete, Evelyne Ruchti, Greta Limoni, Marine Van Campenhoudt, Samuel Bourgeat, Petra Henklein, Christian Gilissen, Bregje W van Bon, Rolph Pfundt, Marjolein H Willemsen, Jolanda H Schieving, Emanuela Leonardi, Fiorenza Soli, Alessandra Murgia, Hui Guo, Qiumeng Zhang, Kun Xia, Christina R Fagerberg, Christoph P Beier, Martin J Larsen, Irene Valenzuela, Paula Fernández-Álvarez, Shiyi Xiong, Robert Śmigiel, Vanesa López-González, Lluís Armengol, Manuela Morleo, Angelo Selicorni, Annalaura Torella, Moira Blyth, Nicola S Cooper, Valerie Wilson, Renske Oegema, Yvan Herenger, Aurore Garde, Ange-Line Bruel, Frederic Tran Mau-Them, Alexis BR Maddocks, Jennifer M Bain, Musadiq A Bhat, Gregory Costain, Peter Kannu, Ashish Marwaha, Neena L Champaigne, Michael J Friez, Ellen B Richardson, Vykuntaraju K Gowda, Varunvenkat M Srinivasan, Yask Gupta, Tze Y Lim, Simone Sanna-Cherchi, Bruno Lemaitre, Toshiyuki Yamaji, Kentaro Hanada, John E Burke, Ana Marjia Jakšić, Brian D McCabe, Paolo De Los Rios, Thorsten Hornemann, Giovanni D’Angelo, Vincenzo A Gennarino
Publication date
2023/5/15
Journal
The Journal of clinical investigation
Volume
133
Issue
10
Publisher
American Society for Clinical Investigation
Description
Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are associated with intellectual disability, but the pathogenic mechanism remains obscure. Here, we characterize 31 individuals with de novo missense variants in CERT1. Several variants fall into a previously uncharacterized dimeric helical domain that enables CERT homeostatic inactivation, without which sphingolipid production goes unchecked. The clinical severity reflects the degree to which CERT autoregulation is disrupted, and inhibiting CERT pharmacologically corrects morphological and motor abnormalities in a Drosophila model of the disease, which we call ceramide transporter (CerTra) syndrome. These findings uncover a central role for CERT …
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Scholar articles
C Gehin, MA Lone, W Lee, L Capolupo, S Ho… - The Journal of clinical investigation, 2023