COPPER ZINC SUPEROXIDE-DISMUTASE-1 AND SPORADIC AMYOTROPHIC-LATERAL-SCLEROSIS - ANALYSIS OF 155 CASES AND IDENTIFICATION OF A NOVEL INSERTION MUTATION/
M. Jackson et al., COPPER ZINC SUPEROXIDE-DISMUTASE-1 AND SPORADIC AMYOTROPHIC-LATERAL-SCLEROSIS - ANALYSIS OF 155 CASES AND IDENTIFICATION OF A NOVEL INSERTION MUTATION/, Annals of neurology, 42(5), 1997, pp. 803-807
Amyotrophic lateral sclerosis (ALS) is a progressive paralytic disorde
r resulting from the degeneration of motor neurons in the brain and sp
inal cord and leading to death within 5 years of symptom onset. The gr
eat majority of ALS cases are sporadic, with the familiar form (FALS)
representing fewer than 10% of all cases. Mutations in the copper/zinc
superoxide dismutase 1 (SOD-1) gene have previously been identified a
s the underlying cause of approximately 20% of FALS cases. As the fami
lial and sporadic forms of the disease are clinically similar, we have
sought to determine whether such mutations in SOD-1 underlie any spor
adic ALS cases. We have screened 155 sporadic cases by single-strand c
onformation polymorphism and have identified 4 sporadic cases that pos
sess point mutations in exon 4 of the SOD-1 gene. Two of these mutatio
ns are identical to those previously reported in FALS cases. One mutat
ion is novel, resulting in a frameshift at Val(118) due to the replace
ment of G (first base in the last codon of exon 4) by AAAAC. This muta
tion results in a truncated SOD-1 protein due to the introduction of a
stop codon three residues into exon 5.