Pathogenic mutations causing LBSL affect mitochondrial aspartyl-tRNA synthetase in diverse ways.
Biochem J
; 450(2): 345-50, 2013 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-23216004
ABSTRACT
The autosomal recessive white matter disorder LBSL (leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation) is caused by mutations in DARS2, coding for mtAspRS (mitochondrial aspartyl-tRNA synthetase). Generally, patients are compound heterozygous for mutations in DARS2. Many different mutations have been identified in patients, including several missense mutations. In the present study, we have examined the effects of missense mutations found in LBSL patients on the expression, enzyme activity, localization and dimerization of mtAspRS, which is important for understanding the cellular defect underlying the pathogenesis of the disease. Nine different missense mutations were analysed and were shown to have various effects on mtAspRS properties. Several mutations have a direct effect on the catalytic activity of the enzyme; others have an effect on protein expression or dimerization. Most mutations have a clear impact on at least one of the properties of mtAspRS studied, probably resulting in a small contribution of the missense variants to the mitochondrial aspartylation activity in the cell.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aspartato-tRNA Ligase
/
Mutação de Sentido Incorreto
/
Doenças Mitocondriais
/
Leucoencefalopatias
/
Mitocôndrias
Limite:
Humans
Idioma:
En
Revista:
Biochem J
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Holanda