Three novel mutations and two variants in the gene for Cu/Zn superoxide dismutase in familial amyotrophic lateral sclerosis

• Published in: Neuromuscular disorders : NMD 1996-10, Vol.6 (5), p.361-366
• Main Authors: Hosler, Betsy A., Nicholson, Garth A., Sapp, Peter C., Chin, Wendy, Orrell, Richard W., De Belleroche, Jackie S., Esteban, Jesus, Hayward, Lawrence J., McKenna-Yasek, Diane, Yeung, Leone, Cherryson, Annia K., Dench, Joanne E., Wilton, Steve D., Laing, Nigel G., Horvitz, H.Robert, Brown, Robert H.
• Format: Article
• Language: English
• Subjects: Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - enzymology; Amyotrophic Lateral Sclerosis - genetics; Family Health; Humans; mutation; neuromuscular disease; Point Mutation - genetics; Polymorphism, Genetic; Polymorphism, Single-Stranded Conformational; Sequence Analysis, DNA; superoxide dismutase; Superoxide Dismutase - genetics
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/0960-8966(96)00353-7

Autosomal dominant inheritance is exhibited by about 10% of cases of amyotrophic lateral sclerosis (ALS), a paralytic disorder characterized by death of motor neurons in the brain and spinal cord. A subgroup of these familial cases are linked to mutations in the gene which codes for Cu/Zn superoxide dismutase (SOD1). We report three additional mutations occurring in the SOD1 gene in ALS patients and two single base pair variant changes. The single base pair change in an ALS family causes a glycine 93 to valine substitution, which is the fifth distinct amino acid change reported for the glycine 93 residue. One missense mutation in exon 5 would substitute neutral valine for the negatively-charged aspartate 124 (aspartate 124 to valine). An individual with an apparently sporadic case of ALS carries a three base pair deletion in exon 5 of the SOD1 gene. These three mutations bring to 38 the total number of distinct SOD1 mutations associated with familial ALS.