SPTLC2 variants are associated with early-onset ALS and FTD due to aberrant sphingolipid synthesis.

ABSTRACT:

Objective

Amyotrophic lateral sclerosis (ALS) is a devastating, incurable neurodegenerative disease. A subset of ALS patients manifests with early-onset and complex clinical phenotypes. We aimed to elucidate the genetic basis of these cases to enhance our understanding of disease etiology and facilitate the development of targeted therapies.

Methods

Our research commenced with an in-depth genetic and biochemical investigation of two specific families, each with a member diagnosed with early-onset ALS (onset age of <40 years). This involved whole-exome sequencing, trio analysis, protein structure analysis, and sphingolipid measurements. Subsequently, we expanded our analysis to 62 probands with early-onset ALS and further included 440 patients with adult-onset ALS and 1163 he

SUBMITTER: Naruse H 

PROVIDER: S-EPMC11021611 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature