Recurrent de-novo gain-of-function mutation in SPTLC2 confirms dysregulated sphingolipid production to cause juvenile amyotrophic lateral sclerosis.
Maike F DohrnDanique BeijerMuseer A LoneElif BayraktarPiraye OflazerRotem OrbachSandra DonkervoortA Reghan FoleyAubrey RoseMichael LyonsRaymond J LouieKenneth GableTeresa DunnSitong ChenMatt C DanziMatthis SynofzikCarsten G BönnemannAyse Nazli BasakThorsten HornemannStephan ZuchnerPublished in: Journal of neurology, neurosurgery, and psychiatry (2023)
represents a new Mendelian ALS gene, highlighting a key role of dysregulated sphingolipid synthesis in the pathogenesis of juvenile ALS. Given the direct interaction of SPTLC1 and SPTLC2, this knowledge might open new therapeutic avenues for motor neuron diseases.