Biallelic DMXL2 mutations impair autophagy and cause Ohtahara syndrome with progressive course

Alessandro Esposito, Antonio Falace, Matias Wagner, Moran Gal, Davide Mei, Valerio Conti, Tiziana Pisano, Davide Aprile, Maria Sabina Cerullo, Antonio De Fusco, Silvia Giovedì, Annette Seibt, Daniella Magen, Tilman Polster, Ayelet Eran, Sarah L Stenton, Chiara Fiorillo, Sarit Ravid, Ertan Mayatepek, Hava HafnerSaskia Wortmann, Erez Y Levanon, Carla Marini, Hanna Mandel, Fabio Benfenati, Felix Distelmaier, Anna Fassio, Renzo Guerrini

Research output: Contribution to journalArticle

Abstract

Esposito et al. identify biallelic loss-of-function mutations in DMXL2, encoding a v-ATPase regulatory protein, in three sibling pairs exhibiting Ohtahara syndrome with a progressive course. Patient-derived fibroblasts and Dmxl2-silenced mouse hippocampal neurons show defective lysosomal function and autophagy, resulting in the latter in impaired neuronal development and synapse formation.
Original languageEnglish
Pages (from-to)3876-3891
Number of pages16
JournalBrain
Volume142
Issue number12
DOIs
Publication statusPublished - 2019

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Esposito, A., Falace, A., Wagner, M., Gal, M., Mei, D., Conti, V., Pisano, T., Aprile, D., Cerullo, M. S., De Fusco, A., Giovedì, S., Seibt, A., Magen, D., Polster, T., Eran, A., Stenton, S. L., Fiorillo, C., Ravid, S., Mayatepek, E., ... Guerrini, R. (2019). Biallelic DMXL2 mutations impair autophagy and cause Ohtahara syndrome with progressive course. Brain, 142(12), 3876-3891. https://doi.org/10.1093/brain/awz326