[Different clinical phenotypes of siblings with familial amyotrophic lateral sclerosis showing Cys146Arg point mutation of superoxide dismutase 1 gene].

We reported different clinical phenotypes of siblings with familial amyotrophic lateral sclerosis (FALS) showing Cys146Arg point mutation of superoxide dismutase 1 (SOD1) gene. They showed differences in disease onset of age, progression and severity. The propositus, a 50-year old woman, had muscle wasting and weakness in right lower leg with dysesthesia at the onset, which showed slow progression without other neurological symptoms until 2 years after the onset when bulbar palsy appeared. She has been alive for 3.5 years after the onset. In contrast, a 61-year old man, elder brother of the propositus, had bulbar palsy at the onset, which showed rapid progression along with muscle weakness and wasting of upper extremities. Two years after the onset, he died due to respiratory failure. Detailed clinical features of FALS with Cys146Arg mutation of SOD1 have not been reported. Our cases suggest that FALS with the same SOD1 mutation could show variable clinical feature and course, and that some factors other than SOD1 mutation should be considered for the pathogenesis of FALS.