Progressive myoclonic epilepsy type 8 due to CERS1 deficiency: a novel mutation with prominent ataxia

• Autor(a) principal: Godeiro Junior, Clécio de Oliveira
• Data de Publicação: 2018
• Outros Autores: Vale, Thiago Cardoso, Afonso, Cintia Oliveira de Melo, Kok, Fernando, Pedroso, José Luiz, Barsottini, Orlando Graziani
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRN
• Texto Completo: https://repositorio.ufrn.br/handle/123456789/52933; https://doi.org/10.1002/mdc3.12610
• topic: ataxia; myoclonus; epilepsy; progressive myoclonic epilepsy

Progressive myoclonic epilepsy (PME) is a heterogeneous groupof disorders characterized by myoclonus, tonic-clonic seizures,and progressive neurological dysfunction, including cognitiveimpairment and taxia. PME type 8 has recently been linked toa mutation inCERS1, the gene encoding ceramide synthase 1(Cers1), a transmembrane protein of the endoplasmic reticulumthat catalyzes the biosynthesis of C18-ceramides. Ceramides arethe precursors to complex sphingolipids, which are lipids with acommon sphingoid base (also termed long chain base) backbonethat plays an essential role in cell signaling, growth, proliferation,differentiation, and apoptosis. In the central nervous system, themost highly expressed ceramide synthase is Cers1, which is partic-ularly present in neurons of neocortex, hippocampus, and cere-bellum. Diminished levels of ceramides and sphingolipidscontaining very long-chain fatty acids have been associated withmany neurodegenerative disorders, including cerebellar Purkinjecell neurodegeneration. In addition, deficiency of Cers functionhave also been linked to accumulation of lipofuscin with ubiqui-tylated proteins in many brain regions.