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Introduction
Juvenile amyotrophic lateral sclerosis (JALS) is a rare and severe motor neuron disease defined by an onset before the age of 25 with currently no available therapy. Only a few genes have been linked to JALS such as ALS2, FUS, SETX, SPG11, SIGMAR1, and more recently SPTLC1. This gene encodes one of the subunits of serine palmitoyltransferase (SPT), which is the first enzyme for de novo sphingolipid biosynthesis.1 Initially, SPTLC1 was a known cause of hereditary sensory and autonomic neuropathy, type 1A.2 In 2021, Johnson et al 3 and Mohassel et al 4 extended the phenotype associated with this gene by reporting several mutations of SPTLC1 in patients with JALS.
Methods
We performed molecular analysis of 1130 patients with ALS, with 50 of them meeting the criteria for juvenile ALS. Plasma lipid profile of patients with SPTLC1 mutation were analysed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) and tandem mass spectrometry (MS/MS).
Results
We identified a total of five individuals harbouring the heterozygous already known pathogenic SPTLC1 (NM_006415.4): c.115_117del, p.(Leu39del) variant (figure 1). Analysis of the single-nucleotide polymorphisms (SNPs) surrounding the mutation allowed us to confidently exclude the possibility of a founder effect (online supplemental material 1).
Supplemental material
Footnotes
Contributors Conceptualisation: CGu. Methodology: CGu. Three-dimensional modelling: J-CD and PP. Formal analysis: CGu, DC, JR, KM, LJ and SM. Investigation: OF, CGo, A-MG; RJM, EDLC, FS and MdMA. Writing—original draft preparation: GC. Writing—review and editing: GC, DC, EDLC, FS, KM, OF and SM. All authors have read and agreed to the published version of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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