PFN1 mutations are rare in Han Chinese populations with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown pathophysiological mechanisms. Profilin 1 gene (PFN1) has been identified as a causative gene, which accounts for 1% to 2% of familial ALS. In this study, we investigated the mutation spectrum of PFN1 in Chinese patients with ALS. A total of 550 ALS patients (including 540 sporadic ALS [SALS] and 10 familial ALS) from the Department of Neurology, West China Hospital of Sichuan University, were recruited for the study. From the same region, 545 healthy control individuals (HC) were recruited as a control group. The encoding regions of the PFN1 gene were screened by direct sequencing. Novel candidate mutations or variations were confirmed by polymerase chain reaction-restriction fragment length polymorphism. A novel nonsynonymous p.R136W mutation was identified in an early-onset SALS female patient. A novel synonymous mutation p.L88L detected in a late-onset SALS female patient was considered nonpathogenic, as it was also detected in a control subject. No mutations were found in 10 familial ALS patients. Moreover, we found a significant difference in the genotype distribution of reported rs13204 (p.L112L) between SALS patients and HC (p = 0.0030). The frequency of minor allele 'T' of rs13204 in the SALS group was significantly lower than that in HC (p = 0.0040, OR = 0.7270, 95% CI = 0.5848-0.9039). Our results suggest that PFN1 mutation is an uncommon cause of ALS in the Han Chinese population. The SNP rs13204 of the PFN1 gene may have an important function in ALS development. The phenotype of ALS patients with mutantPFN1 gene varies among different genetic backgrounds.