A Novel Variant (Asn177Asp) in SPTLC2 Causing Hereditary Sensory Autonomic Neuropathy Type 1C

This study describes the clinical and neurophysiological phenotype of a German family with a novel SPTCL2 mutation (c.529A  >  G; N177D) associated with HSAN1 and the biochemical characterization of this mutation.) The mutaion was identified in five family members that segregated with the diesease. Patients were characterized genetically and clinically for neurophysiological function. Their plasma sphingolipid profiles were analyzed by LC–MS. The biochemical properties of the mutation were characterized in a cell-based activity assay. Affected family members showed elevated 1-deoxysphingolipid plasma levels. HEK293 cells expressing the N177D SPTLC2 mutant showed increased de novo 1-deoxysphingolipid formation, but also displayed elevated canonical SPT activity and increased C20 sphingoid base production. This study identifies the SPTLC2 N177D variant as a novel disease-causing mutation with increased 1-deoxySL formation and its association with a typical HSAN1 phenotype.
Source: NeuroMolecular Medicine - Category: Neurology Source Type: research