Mutations in all five exons of SOD-1 may cause ALS.
Eight of 38 patients (21%) with familial and 5 of 175 patients (3%) with 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 residues. Hypotheses about the toxic role of mutant SOD-1 in the pathogenesis of ALS must account for this molecular diversity.
Shaw
C E
CE
Department of Clinical Neurosciences, Institute of Psychiatry and King's College School of Medicine and Dentistry, London, United Kingdom.
Enayat
Z E
ZE
Chioza
B A
BA
Al-Chalabi
A
A
Radunovic
A
A
Powell
J F
JF
Leigh
P N
PN
D000328:Adult; D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation; D010375:Pedigree; D013482:Superoxide Dismutase / Q000235:genetics*
D013482:Superoxide Dismutase