A novel ALS SOD1 C6S mutation with implications for aggregation related toxicity and genetic counseling.
Amyotroph Lateral Scler
; 12(3): 215-9, 2011 May.
Article
em En
| MEDLINE
| ID: mdl-21073275
ABSTRACT
In this report we describe an ALS family with a novel missense SOD1 mutation with substitution of serine for cysteine at the sixth amino acid (C6S). This mutation has interesting implications for the role of disulfides in causing disease. After identification of the ALS proband, we examined 17 members of an extended family and performed DNA mutation analysis on 21 family members. The level and activity of SOD1 in C6S carriers and wild-type family members was analyzed in erythrocytes. We found that the C6S mutation results in disease with an autosomal dominant mode of inheritance and markedly reduced penetrance. The S6 mutated protein demonstrates high stability relative to the C6 wild-type protein. The specific dismutation activity of S6 SOD1 is normal. In conclusion, C6S is a novel FALS associated mutation with reduced disease penetrance, long survival time and a phenotype very different from the other SOD1 mutations reported in codon C6. This mutation may provide insight into the role of SOD1 structural changes in disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Superóxido Dismutase
/
Aconselhamento Genético
/
Esclerose Lateral Amiotrófica
/
Mutação
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article