“True” sporadic ALS associated with a novel SOD‐1 mutation

Abstract

Mutations in the Cu/Zn superoxide dismutase gene (SOD-1) are reported in 20% of familial amyotrophic lateral sclerosis (ALS) cases, but no definite report of a mutation in a "truly" sporadic case of ALS has been proved. We present the first case of a novel SOD-1 mutation in a patient with genetically proven sporadic ALS. This mutation (H80A) is believed to alter zinc ligand binding, and its functional significance correlates well with the aggressive clinical course and postmortem findings observed in this patient.

Amyotrophic lateral sclerosis associated with mutations in the CuZn superoxide dismutase gene

“…Transcranial magnetic stimulation of the motor cortex (MEP) in D90A-homozygous patients has revealed greatly prolonged central conduction latency even early in the disease. In some cases, no MEP response could be detected even though the patient was ambulatory [29,30]. Neurophysiologic studies have provided evidence that intracortical inhibitory circuits may be selectively preserved in D90A-homozygous patients compared with increased cortical excitability in patients without SOD1 mutations.…”

“…The following SOD1 mutations have been reported in patients diagnosed as apparent SALS: A4V, L8V, G12R, V14G, G16S, N19S, E21K, H48Q, C57R, N65S, G72S, D76Y, H80R, L84F, N86S, N86D, A89V, D90A, G93S, A95T, V97L, D101N, S105∆SL, I113T, T116R, V118L, V118KTGPX, E133∆E, K136X, L144F [9,10•,21,22,24,27,28]. The Irish H80R is the only proven de novo mutation occurring in a SALS patient [29]. For the other mutations, a paternity investigation was not performed or the mutant SOD1 allele was inherited through an unaffected parent.…”

Proteins as Sensitive Biomarkers of Human Conditions Associated with Oxidative Stress

“…A variety of markers of oxidative damage, including protein-bound 3-nitrotyrosine, are indeed increased in ALS spinal cords (Cleveland and Rothstein, 2001). Notably there has been presented the first case of a novel Cu/Zn-SOD mutation in a patient with genetically proved sporadic ALS (Alexander et al, 2002).…”

The genetic basis of amyotrophic lateral sclerosis: recent breakthroughs

“…198,199 Exome sequencing in parent-case offspring trios has already been employed for the investigation of de novo mutations in SALS. [200][201][202] To this end, de novo mutations have been found in genes encoding chromatin regulators, including the neuronal chromatin remodeling complex (nBAF) component SS18L1 (also known as CREST). 203 Furthermore, the usage of exome-wide rare variant burden analysis recently resulted in the discovery of TUBA4A mutations in ALS.…”