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- Title
Impairment of ceramide synthesis causes a novel progressive myoclonus epilepsy.
- Authors
Vanni, Nicola; Fruscione, Floriana; Ferlazzo, Edoardo; Striano, Pasquale; Robbiano, Angela; Traverso, Monica; Sander, Thomas; Falace, Antonio; Gazzerro, Elisabetta; Bramanti, Placido; Bielawski, Jacek; Fassio, Anna; Minetti, Carlo; Genton, Pierre; Zara, Federico
- Abstract
Objective Alterations of sphingolipid metabolism are implicated in the pathogenesis of many neurodegenerative disorders. Methods We identified a homozygous nonsynonymous mutation in CERS1, the gene encoding ceramide synthase 1, in 4 siblings affected by a progressive disorder with myoclonic epilepsy and dementia. CerS1, a transmembrane protein of the endoplasmic reticulum (ER), catalyzes the biosynthesis of C18-ceramides. Results We demonstrated that the mutation decreases C18-ceramide levels. In addition, we showed that downregulation of CerS1 in a neuroblastoma cell line triggers ER stress response and induces proapoptotic pathways. Interpretation This study demonstrates that impairment of ceramide biosynthesis underlies neurodegeneration in humans. Ann Neurol 2014;76:206-212
- Publication
Annals of Neurology, 2014, Vol 76, Issue 2, p206
- ISSN
0364-5134
- Publication type
Article
- DOI
10.1002/ana.24170