Superoxide dismutase gene mutations in Italian patients with familial and sporadic amyotrophic lateral sclerosis: identification of three novel missense mutations.

TitleSuperoxide dismutase gene mutations in Italian patients with familial and sporadic amyotrophic lateral sclerosis: identification of three novel missense mutations.
Publication TypeJournal Article
Year of Publication2001
AuthorsGellera, C, Castellotti, B, Riggio, MC, Silani, V, Morandi, L, Testa, D, Casali, C, Taroni, F, Di Donato, S, Zeviani, M, Mariotti, C
JournalNeuromuscul Disord
Volume11
Issue4
Pagination404-10
Date Published2001 May
ISSN0960-8966
KeywordsAdult, Aged, Amino Acid Sequence, Amyotrophic Lateral Sclerosis, Base Sequence, Female, Heterozygote, Homozygote, Humans, Italy, Male, Middle Aged, Molecular Sequence Data, Mutation, Mutation, Missense, Pedigree, Superoxide Dismutase
Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons. The majority of the patients are sporadic cases (SALS), while 5-10% of the patients have a family history of ALS (familial ALS or FALS). Mutations in the gene coding for cytoplasmic Cu/Zn superoxide dismutase (SOD1) have been identified in about 20% of FALS cases. We found SOD1-gene mutations in five of 34 unrelated FALS, and in two of 44 SALS patients. Three FALS patients carried the previously described A4V (two cases) and L84F mutations (one case), while two FALS patients carried new missense mutations: a G12R substitution in exon 1, and a F45C substitution in exon 2, respectively. The newly identified mutations were both associated with a slowly progressive disease course. Two SALS patients carried the homozygous D90A and the heterozygous I113T mutation, respectively. In addition, in one SALS patient we identified an A95T amino acid substitution, that is apparently a non-pathogenic SOD1 variant. Our study increases the number of ALS-associated SOD1 gene mutations.

DOI10.1016/s0960-8966(00)00215-7
Alternate JournalNeuromuscul. Disord.
Citation Key10.1016/s0960-8966(00)00215-7
PubMed ID11369193