A novel TARDBP mutation in an Australian amyotrophic lateral sclerosis kindred.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative 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.
Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord Hospital NSW 2139, Australia.
K L
KL
Williams
J C
JC
Durnall
A D
AD
Thoeng
S T
ST
Warraich
G A
GA
Nicholson
I P
IP
Blair
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000818:Animals; D001315:Australia; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein
D004268:DNA-Binding Proteins