EPT1 mutation causes complicated HSP

Affects myelin sheath that covers nerves


This study establishes the indispensible role of the EPT1 gene in the process of nerve myelination and in the normal function of certain cell lipids.

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Ethanolamine phosphotransferase 1 (EPT1), also known as selenoprotein 1 (SELENOI), is an enzyme that transfers phosphoethanolamine from cytidine diphosphate (CDP)-ethanolamine to lipid acceptors to produce ethanolamine glycerophospholipids such as diacyl-linked phosphatidylethanolamine (PE) and ether linked plasmalogen (plasmenyl-PE). However, to date there has been no analysis of the metabolomic consequence of the mutation of EPT1 on the concentration of ethanolamine glycerophospholipids in mammalian cells.


We studied a patient with severe complicated hereditary spastic paraplegia, sensorineural-deafness, blindness, and seizures. Neuroimaging revealed hypomyelination, followed by brain atrophy mainly in the cerebellum and brainstem. Using whole exome sequencing, we identified a novel EPT1 mutation (exon skipping). In vitro EPT activity as well as the rate of biosynthesis of ethanolamine glycerophospholipids was markedly reduced in cultures of the patient’s skin fibroblasts. Quantification of phospholipids by LC-MS/MS demonstrated reduced levels of several PE species with polyunsaturated fatty acids, such as 38:6, 38:4, 40:6, 40:5, and 40:4. Notably, most plasmenyl-PE species were significantly decreased in the patient’s cells whereas most plasmanyl-choline (plasmanyl-PC) species were increased. Similar findings regarding decreased plasmenyl-PE and increased plasmanyl-PC were obtained using EPT1-KO HeLa cells.


Our data demonstrate for the first time the indispensable role of EPT1 in the myelination process and in neurodevelopment, and in the maintenance of normal homeostasis of ether-linked phospholipids in human.


SOURCE: J Lipid Res. 2018 Mar 2. pii: jlr.P081620. doi: 10.1194/jlr.P081620. [Epub ahead of print] PMID: 29500230


Ethanolamine phosphotransferasa 1 (selenoprotein I) is critical for the neural development and maintenance of plasmalogen in human.


Horibata Y1, Elpeleg O2, Eran A3, Hirabayashi Y4, Savitzki D5, Tal G6, Mandel H6, Sugimoto H7.


1 Dokkyo Medical University School of Medicine, Japan.

2 Hadassah-Hebrew University Medical Center, Israel.

3 Rambam Health Care Campus Haifa, Israel.

4 Molecular Membrane Neuroscience, RIKEN Brain Science Institute, RIKEN, Japan.

5 Pediatric Neurology Unit, Galilee Medical Center, Israel.

6 Metabolic Unit, Rambam Health Care Campus, Rappaport School of Medicine, Israel.

7 Dokkyo Medical University School of Medicine, Japan; [email protected].



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