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New Insights into the Neuromyogenic Spectrum of a Gain of Function Mutation in SPTLC1
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 sphi...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140917/ https://www.ncbi.nlm.nih.gov/pubmed/35627278 http://dx.doi.org/10.3390/genes13050893 |
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author | Kölbel, Heike Kraft, Florian Hentschel, Andreas Czech, Artur Gangfuss, Andrea Mohassel, Payam Nguyen, Chi Stenzel, Werner Schara-Schmidt, Ulrike Preuße, Corinna Roos, Andreas |
author_facet | Kölbel, Heike Kraft, Florian Hentschel, Andreas Czech, Artur Gangfuss, Andrea Mohassel, Payam Nguyen, Chi Stenzel, Werner Schara-Schmidt, Ulrike Preuße, Corinna Roos, Andreas |
author_sort | Kölbel, Heike |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9140917 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91409172022-05-28 New Insights into the Neuromyogenic Spectrum of a Gain of Function Mutation in SPTLC1 Kölbel, Heike Kraft, Florian Hentschel, Andreas Czech, Artur Gangfuss, Andrea Mohassel, Payam Nguyen, Chi Stenzel, Werner Schara-Schmidt, Ulrike Preuße, Corinna Roos, Andreas Genes (Basel) Article 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. MDPI 2022-05-17 /pmc/articles/PMC9140917/ /pubmed/35627278 http://dx.doi.org/10.3390/genes13050893 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kölbel, Heike Kraft, Florian Hentschel, Andreas Czech, Artur Gangfuss, Andrea Mohassel, Payam Nguyen, Chi Stenzel, Werner Schara-Schmidt, Ulrike Preuße, Corinna Roos, Andreas New Insights into the Neuromyogenic Spectrum of a Gain of Function Mutation in SPTLC1 |
title | New Insights into the Neuromyogenic Spectrum of a Gain of Function Mutation in SPTLC1 |
title_full | New Insights into the Neuromyogenic Spectrum of a Gain of Function Mutation in SPTLC1 |
title_fullStr | New Insights into the Neuromyogenic Spectrum of a Gain of Function Mutation in SPTLC1 |
title_full_unstemmed | New Insights into the Neuromyogenic Spectrum of a Gain of Function Mutation in SPTLC1 |
title_short | New Insights into the Neuromyogenic Spectrum of a Gain of Function Mutation in SPTLC1 |
title_sort | new insights into the neuromyogenic spectrum of a gain of function mutation in sptlc1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140917/ https://www.ncbi.nlm.nih.gov/pubmed/35627278 http://dx.doi.org/10.3390/genes13050893 |
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