Novel missense ALDH18A1 variant in a family with autosomal dominant spastic paraplegia.

ABSTRACT:

Objectives

We aim to characterize a novel heterozygous missense variant c.1703A > G/p. (Gln568Arg) in the ALDH18A1 gene, identified in a family with autosomal dominant hereditary spastic paraplegia (HSP). We evaluated clinical, neurophysiological, genetic, fluid biomarkers, and neuroimaging expression in different family members with and without the mutation.

Methods

A comprehensive multimodal evaluation was performed, including neurological examination, motor and sensory conduction studies, transcranial magnetic stimulation, targeted genetic sequencing, biomarker analysis (amino acid profiling and plasma neurofilament light chain levels (pNfL)), and brain and spinal cord MRI. Mutation pathogenicity was assessed using in silico prediction tools and confirmed by segregation a

SUBMITTER: Novarella F 

PROVIDER: S-EPMC12678542 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature