Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis

摘要: Amyotrophic lateral sclerosis (ALS) is a degenerative disorder of motor neurons in the cortex, brainstem and spinal cord. Its cause unknown it uniformly fatal, typically within five years. About 10% cases are inherited as an autosomal dominant trait, with high penetrance after sixth decade. In most instances, sporadic familial ALS (FALS) clinically similar. We have previously shown that some but not all FALS pedigrees disease linked to genetic defect on chromosome 21q (refs 8, 9). Here we report tight linkage between gene encodes cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), homodimeric metalloenzyme catalyzes dismutation toxic anion O2.- O2 H2O2 (ref. 10). Given this potential role free radical toxicity other neurodenegerative disorders, investigated SOD1 candidate FALS. identified 11 different missense mutations 13 families.