3 NOVEL MUTATIONS AND 2 VARIANTS IN THE GENE FOR CU ZN SUPEROXIDE-DISMUTASE IN FAMILIAL AMYOTROPHIC-LATERAL-SCLEROSIS/

Autosomal dominant inheritance is exhibited by about 10% of cases of a myotrophic lateral sclerosis (ALS), a paralytic disorder characterized by death of motor neurons in the brain and spinal cord. A subgroup of these familial cases are linked to mutations in the gene which codes for Cu/Zn superoxide dismutase (SOD1). We report three additional muta tions occurring in the SOD1 gene in ALS patients and two single base p air variant changes. The single base pair change in an ALS family caus es a glycine 93 to valine substitution, which is the fifth distinct am ino acid change reported for the glycine 93 residue. One missense muta tion in exon 5 would substitute neutral valine for the negatively-char ged aspartate 124 (aspartate 124 to valine). An individual with an app arently sporadic case of ALS carries a three base pair deletion in exo n 5 of the SOD1 gene. These three mutations bring to 38 the total numb er of distinct SOD1 mutations associated with familial ALS.