Identification of a novel D109Y mutation in Cu/Zn superoxide dismutase (sod1) gene associated with amyotrophic lateral sclerosis.

We report a novel missense mutation (Asp109Tyr) in exon 4 of the Cu/Zn superoxide dismutase (sod1) gene in a woman with apparently sporadic amyotrophic lateral sclerosis (SALS). Signs of motor deficit appeared at the age of 51 years which progressed over the next 6 years to upper and lower motor neuron disease and death occurred by the age of 57 years. In this mutation, the base change of guanine to thymine at codon 109 of sod1 gene leads to the replacement of aspartic by tyrosine in the protein. This amino acid change in the protein however, did not alter the catalytic activity of the SOD1 enzyme as there was no change in the enzymatic activity of purified SOD1 from the patient's erythrocytes compared to control.