Recurrent de-novo gain-of-function mutation in SPTLC2 confirms dysregulated sphingolipid production to cause juvenile amyotrophic lateral sclerosis.

ABSTRACT:

Background

Amyotrophic lateral sclerosis (ALS) leads to paralysis and death by progressive degeneration of motor neurons. Recently, specific gain-of-function mutations in SPTLC1 were identified in patients with juvenile form of ALS. SPTLC2 encodes the second catalytic subunit of the serine-palmitoyltransferase (SPT) complex.

Methods

We used the GENESIS platform to screen 700 ALS whole-genome and whole-exome data sets for variants in SPTLC2. The de-novo status was confirmed by Sanger sequencing. Sphingolipidomics was performed using liquid chromatography and high-resolution mass spectrometry.

Results

Two unrelated patients presented with early-onset progressive proximal and distal muscle weakness, oral fasciculations, and pyramidal si

SUBMITTER: Dohrn MF 

PROVIDER: S-EPMC10922288 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature