Mutation Screening of TFG in α-Synucleinopathy and Amyotrophic Lateral Sclerosis

Background: Recently, p.R383H in TFG was identified as the disease cause in a family with α-synucleinopathy and amyotrophic lateral sclerosis (ALS). However, no further replication has been conducted in larger cohorts.

Objective: The aim was to explore the genetic role of TFG in α-synucleinopathy and ALS.

Methods: We analyzed the rare protein-coding variants in patients with Parkinson's disease (PD), ALS, multiple system atrophy (MSA), spastic paraplegia (N = 2709), and 7536 controls with whole-exome sequencing.

Results: Nine rare variants were identified in PD and two in MSA. One PD patient carried the same variant p.R383H. Similarly, this patient developed early-onset PD with bradykinesia and rigidity on the left side as the initial symptoms. However, at the gene level, rare variants of TFG were not enriched in patients.

Conclusions: Rare variants of TFG were not enriched in α-synucleinopathy and ALS. However, we could not deny the potential pathogenicity of specific variants such as p.R383H. Further exploration is still necessary. © 2022 International Parkinson and Movement Disorder Society.