Marked intrafamilial phenotypic variation in a family with SOD1 C111Y mutation

Our objectives were to identify the disease-causing mutation in, and report on the clinical features of, a Japanese family that had coexisting phenotypes of amyotrophic lateral sclerosis and spinal muscular atrophy. The family comprised nine patients (six men and three women). We reviewed their clinical records and performed mutation analysis of the copper/zinc superoxide dismutase (SOD1) gene in some of these patients. The patients either had a rapid (n = 7) or an extremely long (n = 2) clinical course. The mean age at onset was 39.0 ± 13.7 years (range 20–68 years). The initial symptoms were bulbar palsy (n = 2), upper (n = 4) or lower (n = 2) limb muscle weakness, or leg cramps (n = 1). The total disease duration varied widely, ranging from one year to > 69 years. We identified a SOD1 C111Y mutation among patients in this family. In conclusion, the family showed a marked intrafamilial phenotypic variation associated with the SOD1 C111Y mutation. Elucidating the biological basis of disease expression in patients with the SOD1 C111Y mutation may provide us with useful information to develop therapeutic approaches and to prevent disease progression.