MUTATIONS IN ALL 5 EXONS OF SOD-1 MAY CAUSE ALS

Eight of 38 patients (21%) with familiar and 5 of 175 patients (3%) wi th sporadic amyotrophic lateral sclerosis (ALS) had missense mutations in the SOD-1 gene. Two novel mutations were identified. One in exon 4 substituting leucine with phenylalanine (L84F) in a familial patient and the second in exon 3 at substituting glycine with serine (G72S) in an ''apparently'' sporadic patient. Over 60 point mutations have now been described in all five exons of SOD-1, involving 43 of the 153 res idues. Hypotheses about the toxic role of mutant SOD-1 in the pathogen esis of ALS must account for this molecular diversity.