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

Abstract 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.