TARDBP p.G376D mutation, found in rapid progressive familial ALS, induces mislocalization of TDP-43

摘要

A 36-year-old male (Patient 1) suffered from progressive head drop and muscle weakness in his upper extremities. Physical examination findings revealed muscle atrophy and weakness in his tongue and distal dominant upper extremities. Fasciculation was observed in his tongue and right upper extremity. Hyperreflexia was observed in four ex- tremities without Babinski response. Needle electromyography showed reduced interference patterns in the upper extremities. Denervation potentials and high-amplitude polyphasic motor unit potentials were detected in the biceps brachii. Routine blood analysis, cerebrospinal fluid analysis, and brain and spinal MRIs revealed no abnormalities. In accordance with the revised El Escorial criteria [4], we diagnosed him with clinically possible ALS. One year after onset, he died from re- spiratory failure.