Study On Characteristics Of Mutation Of TARDBP Gene In Chinese Patients With Amyotrophic Lateral Sclerosis

Objective TARDBP mutations have been reported in patients with amyotrophic lateral sclerosis (ALS) in different populations except Chinese. The present aim was to investigate the association between TARDBP mutations and Chinese patients with ALS. Methods 71 SALS patients and 5 FALS families with non-SOD1 mutations were screened for TARDBP mutations via direct sequencing. Results A novel heterozygous variation, Ser292Asn(c.875G>A), was identified in the proband and 4 asymptomatic relatives including the children of the dead patient from a FALS family. Thus the dead patient, the proband's brother, was speculated to carry Ser292Asn though his sample was unavailable to the detection. This variation was not found in 200 unrelated control subjects. A homology search of the TDP-43 protein in different species demonstrated that it was highly conserved. Therefore, Ser292Asn is predicted to be a pathogenic mutation. In addition, we have found two silent mutations (p.Gly40Gly and p.Ala366Ala) and one novel polymorphism (239-18t>c). Conclusions The present data have extended the spectrum of TARDBP mutations and polymorphisms, also, supported the pathological role of TDP-43 in Chinese ALS patients.