Genetic and clinical features of Chinese sporadic amyotrophic lateral sclerosis patients with TARDBP mutations

OBJECTIVES: To investigate the genetic and clinical features of Chinese sporadic amyotrophic lateral sclerosis (SALS) patients with TARDBP mutations, we carried out a genetic analysis in a cohort of 391 SALS patients and explored the clinical manifestations of patients with TARDBP variants. MATERIALS AND METHODS: The coding region of all five coding exons of TARDBP, exons 2–6, were sequenced for mutations in 391 Chinese SALS patients. The clinical features of patients with TARDBP mutations were described and compared with cases in literatures. RESULTS: Two missense mutations in TARDBP gene, c.1132A > G (p.N378D) and c.1147A > G (p.I383V), were detected in three cases, showing a low frequency (0.77%, 3/391) of TARDBP missense mutations in Chinese SALS patients. Based on a retrospective analysis of literatures, p.N378D mutation mainly presents a phenotype of early onset, whereas p.I383V mutation presents pure ALS or ALS alongside semantic variant primary progressive aphasia (svPPA), a type of frontotemporal dementia (FTD). CONCLUSIONS: Our results demonstrate that TARDBP mutation is a rare cause of Chinese SALS patients and expand the spectrum of phenotype. It is implied that genetic analysis of SALS patients plays a crucial role in uncovering the cause of disease, especially for cases developing early onset or alongside FTD.