Abstract
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease associated with a positive familial history in 5-10% of ALS cases. Mutations in the superoxide dismutase-1 (SOD1) gene have been found in 12%-23% of patients diagnosed with familial ALS. Here we report a novel mutation in exon 4 of SOD1 gene in a 55-year-old ALS patient belonging to a large Italian family with ALS first clinically described in 1968. In the family the clinical presentation was characterized by relatively early age of onset, spinal onset with proximal distribution weakness, bulbar involvement and a rapid disease course. Molecular analysis showed a heterozygous mutation at codon 106 resulting in a substitution of phenylalanine for leucine in the SOD1 protein (L106F). In analogy with the previously reported L106V mutation, we propose that the L106F causes a relevant destabilization of the protein chain around the mutation site, able to affect the SOD1 monomer and dimer structures suggesting a pathogenic role for this novel mutation.
| Original language | English |
|---|---|
| Pages (from-to) | 112-115 |
| Number of pages | 4 |
| Journal | Journal of the Neurological Sciences |
| Volume | 293 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - Jun 15 2010 |
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Keywords
- Amyotrophic Lateral Sclerosis
- Familial ALS
- Mutation
- Protein structural modelling
- Superoxide dismutase 1 (SOD1) gene
ASJC Scopus subject areas
- Clinical Neurology
- Neurology
Cite this
Severe familial ALS with a novel exon 4 mutation (L106F) in the SOD1 gene. / Battistini, Stefania; Ricci, Claudia; Lotti, Enrico Maria; Benigni, Michele; Gagliardi, Stella; Zucco, Riccardo; Bondavalli, Massimo; Marcello, Norina; Ceroni, Mauro; Cereda, Cristina.
In: Journal of the Neurological Sciences, Vol. 293, No. 1-2, 15.06.2010, p. 112-115.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Severe familial ALS with a novel exon 4 mutation (L106F) in the SOD1 gene
AU - Battistini, Stefania
AU - Ricci, Claudia
AU - Lotti, Enrico Maria
AU - Benigni, Michele
AU - Gagliardi, Stella
AU - Zucco, Riccardo
AU - Bondavalli, Massimo
AU - Marcello, Norina
AU - Ceroni, Mauro
AU - Cereda, Cristina
PY - 2010/6/15
Y1 - 2010/6/15
N2 - Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease associated with a positive familial history in 5-10% of ALS cases. Mutations in the superoxide dismutase-1 (SOD1) gene have been found in 12%-23% of patients diagnosed with familial ALS. Here we report a novel mutation in exon 4 of SOD1 gene in a 55-year-old ALS patient belonging to a large Italian family with ALS first clinically described in 1968. In the family the clinical presentation was characterized by relatively early age of onset, spinal onset with proximal distribution weakness, bulbar involvement and a rapid disease course. Molecular analysis showed a heterozygous mutation at codon 106 resulting in a substitution of phenylalanine for leucine in the SOD1 protein (L106F). In analogy with the previously reported L106V mutation, we propose that the L106F causes a relevant destabilization of the protein chain around the mutation site, able to affect the SOD1 monomer and dimer structures suggesting a pathogenic role for this novel mutation.
AB - Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease associated with a positive familial history in 5-10% of ALS cases. Mutations in the superoxide dismutase-1 (SOD1) gene have been found in 12%-23% of patients diagnosed with familial ALS. Here we report a novel mutation in exon 4 of SOD1 gene in a 55-year-old ALS patient belonging to a large Italian family with ALS first clinically described in 1968. In the family the clinical presentation was characterized by relatively early age of onset, spinal onset with proximal distribution weakness, bulbar involvement and a rapid disease course. Molecular analysis showed a heterozygous mutation at codon 106 resulting in a substitution of phenylalanine for leucine in the SOD1 protein (L106F). In analogy with the previously reported L106V mutation, we propose that the L106F causes a relevant destabilization of the protein chain around the mutation site, able to affect the SOD1 monomer and dimer structures suggesting a pathogenic role for this novel mutation.
KW - Amyotrophic Lateral Sclerosis
KW - Familial ALS
KW - Mutation
KW - Protein structural modelling
KW - Superoxide dismutase 1 (SOD1) gene
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U2 - 10.1016/j.jns.2010.03.009
DO - 10.1016/j.jns.2010.03.009
M3 - Article
VL - 293
SP - 112
EP - 115
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
IS - 1-2
ER -