A novel TARDBP mutation in an Australian amyotrophic lateral sclerosis kindred

作者：Williams K L; Durnall J C; Thoeng A D; Warraich S T; Nicholson G A; Blair I P^*

来源：Journal of Neurology Neurosurgery and Psychiatry, 2009, 80(11): 1286-1288.

DOI：10.1136/jnnp.2008.163261

Amyotrophic lateral sclerosis (ALS) is a fatal neurode-generative disorder that causes loss of motor neurons. A pathological hallmark of ALS is the presence of ubiquitinated TAR DNA binding protein (TDP-43) inclusions in the cytoplasm of affected cells. Rare pathogenic mutations within the gene TARDBP that encode TDP-43 were recently reported in ALS but their functional consequences are unknown. To further investigate the pathogenic role of TDP-43 in ALS, a mutation analysis of TARDBP was performed in an Australian cohort of 74 sporadic and 30 familial ALS cases. A novel familial ALS mutation in TDP-43 was identified that substitutes a highly conserved residue (G294V) and is predicted to disrupt the glycine rich domain in the C terminus, a region that plays a role in RNA binding and is required for the exon skipping activity of TDP-43.

• 出版日期2009-11