A NEW VARIANT CU ZN SUPEROXIDE-DISMUTASE (VAL(7)-]GLU) DEDUCED FROM LYMPHOCYTE MESSENGER-RNA SEQUENCES FROM JAPANESE PATIENTS WITH FAMILIALAMYOTROPHIC-LATERAL-SCLEROSIS/

We have identified a new mutant Cu/Zn superoxide dismutase (SOD1) dedu ced from the nucleotide sequences of peripheral blood lymphocyte mRNA from Japanese patients with familial amyotrophic lateral sclerosis (FA LS). Sequence analysis of reverse transcriptase-initiated PCR amplifie d mRNA revealed a heterozygosity indicative of one normal allele and o ne variant allele with a T-->A transversion. This base change led to r eplacement of valine by glutamic acid at position 7 of 153-residue SOD 1 molecule, and produced a new restriction site for Alu I in the exon 1. Restriction fragment length polymorphism analysis confirmed the lin kage of this mutation with this type of FALS. Both enzymatic activity and protein of the SOD1 were reduced in red blood cells from the patie nt. (C) 1994 Academic Press, Inc.