@Article{duepublico_mods_00076605, author = {K{\"o}lbel, Heike and Kraft, Florian and Hentschel, Andreas and Czech, Artur and Gangfuss, Andrea and Mohassel, Payam and Nguyen, Chi and Stenzel, Werner and Schara-Schmidt, Ulrike and Preu{\ss}e, Corinna and Roos, Andreas}, title = {New Insights into the Neuromyogenic Spectrum of a Gain of Function Mutation in SPTLC1}, year = {2022}, month = {May}, day = {17}, keywords = {SPTLC1; juvenile ALS; HSAN1A; proteomic profiling; serine palmitoyltransferase}, abstract = {Serine palmitoyltransferase long chain base subunit 1 (SPTLC1) encodes a serine palmitoyltransferase (SPT) resident in the endoplasmic reticulum (ER). Pathological SPTLC1 variants cause a form of hereditary sensory and autonomic neuropathy (HSAN1A), and have recently been linked to unrestrained sphingoid base synthesis, causing a monogenic form of amyotrophic lateral sclerosis (ALS). It was postulated that the phenotypes associated with dominant variants in SPTLC1 may represent a continuum between neuropathy and ALS in some cases, complicated by additional symptoms such as cognitive impairment. A biochemical explanation for this clinical observation does not exist. By performing proteomic profiling on immortalized lymphoblastoid cells derived from one patient harbouring an alanine to serine amino acid substitution at position 20, we identified a subset of dysregulated proteins playing significant roles in neuronal homeostasis and might have a potential impact on the manifestation of symptoms. Notably, the identified p.(A20S)-SPTLC1 variant is associated with decrease of transcript and protein level. Moreover, we describe associated muscle pathology findings, including signs of mild inflammation accompanied by dysregulation of respective markers on both the protein and transcript levels. By performing coherent anti-Stokes Raman scattering microscopy, presence of protein and lipid aggregates could be excluded.}, note = {<p>K{\"o}lbel, H., Kraft, F., Hentschel, A., Czech, A., Gangfuss, A., Mohassel, P., Nguyen, C., Stenzel, W., Schara-Schmidt, U., Preu{\ss}e, C., {\&}amp; Roos, A. (2022). New Insights into the Neuromyogenic Spectrum of a Gain of Function Mutation in SPTLC1. <em>Genes</em>, <em>13</em>, 893. <a href="https://doi.org/10.3390/genes13050893">https://doi.org/10.3390/genes13050893</a></p> <p>Published: 17 May 2022</p>}, note = {Version of Record / Verlagsversion}, note = {<p>The publication of this article was supported by the Publication Fund of the University of Duisburg-Essen.</p>}, doi = {10.3390/genes13050893}, url = {https://duepublico2.uni-due.de/receive/duepublico_mods_00076605}, url = {https://doi.org/10.3390/genes13050893}, file = {:https://duepublico2.uni-due.de/servlets/MCRFileNodeServlet/duepublico_derivate_00076337/genes_2022-13-00893.pdf:PDF}, language = {en} }