SPTLC2 variants are associated with early-onset ALS and FTD due to aberrant sphingolipid synthesis.
Hiroya NaruseHiroyuki IshiuraKayoko EsakiJun MitsuiWataru SatakePeter GreimelNanoka ShingaiYuka MachinoYasumasa KokuboHirotoshi HamaguchiTetsuya OdaTomoko IkkakuIchiro YokotaYuji TakahashiYuta SuzukiTakashi MatsukawaJun GotoKishin KohYoshihisa TakiyamaShinichi MorishitaTakeo YoshikawaShoji TsujiTatsushi TodaPublished in: Annals of clinical and translational neurology (2024)
Our study revealed novel SPTLC2 variants in patients with early-onset ALS exhibiting frontotemporal dementia. The combination of genetic evidence and the observed elevation in plasma ceramide levels establishes a crucial link between dysregulated sphingolipid metabolism and ALS pathogenesis. These findings expand our understanding of ALS's genetic diversity and highlight the distinct roles of gene defects within SPT subunits in its development.