Autosomal recessive progressive myoclonus epilepsy due to impaired ceramide synthesis

Edoardo Ferlazzo, Pasquale Striano, Domenico Italiano, Tiziana Calarese, Sara Gasparini, Nicola Vanni, Floriana Fruscione, Pierre Genton, Federico Zara

Research output: Contribution to journalReview article

Abstract

Autosomal recessive progressive myoclonus epilepsy due to impaired ceramide synthesis is an extremely rare condition, so far reported in a single family of Algerian origin presenting an unusual, severe form of progressive myoclonus epilepsy characterized by myoclonus, generalized tonic-clonic seizures and moderate to severe cognitive impairment, with probable autosomal recessive inheritance. Disease onset was between 6 and 16 years of age. Genetic study allowed to identify a homozygous nonsynonymous mutation in CERS1, the gene encoding ceramide synthase 1, a transmembrane protein of the endoplasmic reticulum (ER), catalyzes the biosynthesis of C18-ceramides. The mutation decreased C18-ceramide levels. In addition, downregulation of CerS1 in neuroblastoma cell line showed activation of ER stress response and induction of proapoptotic pathways. This observation demonstrates that impairment of ceramide biosynthesis underlies neurodegeneration in humans.

Original languageEnglish
Pages (from-to)S120-S127
JournalEpileptic Disorders
Volume18
DOIs
Publication statusPublished - 2016

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Keywords

  • Ceramide synthase
  • Epilepsy
  • ER stress response
  • Neurodegeneration
  • Progressivemyoclonus epilepsies

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Ferlazzo, E., Striano, P., Italiano, D., Calarese, T., Gasparini, S., Vanni, N., Fruscione, F., Genton, P., & Zara, F. (2016). Autosomal recessive progressive myoclonus epilepsy due to impaired ceramide synthesis. Epileptic Disorders, 18, S120-S127. https://doi.org/10.1684/epd.2016.0857