Novel mutations in SCO1 as a cause of fatal infantile encephalopathy and lactic acidosis.
Hum Mutat
; 34(10): 1366-70, 2013 Oct.
Article
em En
| MEDLINE
| ID: mdl-23878101
ABSTRACT
Isolated cytochrome c oxidase (COX) deficiency is a common cause of mitochondrial disease, yet its genetic basis remains unresolved in many patients. Here, we identified novel compound heterozygous mutations in SCO1 (p.M294V, p.Val93*) in one such patient with fatal encephalopathy. The patient lacked the severe hepatopathy (p.P174L) or hypertrophic cardiomyopathy (p.G132S) observed in previously reported SCO1 cases, so we investigated whether allele-specific defects in SCO1 function might underlie the genotype-phenotype relationships. Fibroblasts expressing p.M294V had a relatively modest decrease in COX activity compared with those expressing p.P174L, whereas both SCO1 lines had marked copper deficiencies. Overexpression of known pathogenic variants in SCO1 fibroblasts showed that p.G132S exacerbated the COX deficiency, whereas COX activity was partially or fully restored by p.P174L and p.M294V, respectively. These data suggest that the clinical phenotypes in SCO1 patients might reflect the residual capacity of the pathogenic alleles to perform one or both functions of SCO1.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acidose Láctica
/
Atrofias Olivopontocerebelares
/
Proteínas de Membrana
/
Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Humans
/
Infant
Idioma:
En
Revista:
Hum Mutat
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Canadá