Mutation in TAR DNA binding protein-43 (TDP-43) gene in familial amyotrophic lateral sclerosis with Bunina bodies

Osamu Onodera¹⁾, Akio Yokoseki²⁾, Chun-Feng Tan³⁾, Atsushi Shiga²⁾, Hiroyuki Kaneko²⁾, Asako Tagawa²⁾, Koichi Okamoto⁴⁾, Masatoyo Nisizawa²⁾, Hitoshi Takahashi³⁾

¹⁾Department of Molecular neuroscience Resource Branch for Brain Disease Research, Niigata University
²⁾Department of Neurology, Niigata University
³⁾Department of Pathology, Brain Research Institute, Niigata University
⁴⁾Department of Neurology Gunma University Graduate School of Medicine

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. Accumulating evidence has shown that TDP-43 is the disease protein in ALS and frontotemporal lobar degeneration. We have recently reported a familial ALS with TDP-43-positive skein-like inclusions and TDP-43-negative Bunina bodies in the lower motor neurons, which is indistinguishable from sporadic ALS. In three affected individuals in two generations in the family, we found a mutation in TDP-43. Our result provides a new insight into the molecular pathogenesis of ALS.

Address correspondence to Dr. Osamu Onodera M.D., Ph.D., Department of Molecular Neuroscience Resource Branch for Brain Disease Research, Niigata University (1-757 Asahimachi-dori, Chuo-Ku, Niigata 951-8585, Japan)