Impairment of ceramide synthesis causes a novel progressive myoclonus epilepsy
Annals of neurology, 2014•Wiley Online Library
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 …
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 …
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
Wiley Online Library