Association between novel TARDBP mutations and Chinese patients with amyotrophic lateral sclerosis

• Main Authors: Zheng Qiao-Juan (Author), Qiao Kai (Author), Chen Yan (Author), Wu Jian-Jun (Author), Sun Yi-Min (Author), Wang Jin-Yang (Author), Xiong Hui-Ling (Author), Zhao Gui-xian (Author), Wu Zhi-Ying (Author)
• Format: Book
• Published: BMC, 2010-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/1471-2350-11-8; 1471-2350
• Keywords: Internal medicine; RC31-1245; Genetics; QH426-470
• Source: BMC Medical Genetics, Vol 11, Iss 1, p 8 (2010)

<p>Abstract</p> <p>Background</p> <p><it>TARDBP </it>mutations have been reported in patients with amyotrophic lateral sclerosis (ALS) in different populations except Chinese. The present aim is to investigate the association between <it>TARDBP </it>mutations and Chinese patients with ALS.</p> <p>Methods</p> <p>71 SALS patients and 5 FALS families with non-<it>SOD1 </it>mutations were screened for <it>TARDBP </it>mutations via direct sequencing.</p> <p>Results</p> <p>A novel heterozygous variation, Ser292Asn (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. Also, it was predicted to be deleterious to protein function with SIFT-calculated probabilities of 0.00. Therefore, Ser292Asn is predicted to be a pathogenic mutation. In addition, we have found two silent mutations (Gly40Gly and Ala366Ala) and one novel polymorphism (239-18t>c).</p> <p>Conclusions</p> <p>The present data have extended the spectrum of <it>TARDBP </it>mutations and polymorphisms, and supported the pathological role of TDP-43 in Chinese ALS patients.</p>