Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome.
J Med Genet
; 41(1): 14-7, 2004 Jan.
Article
en En
| MEDLINE
| ID: mdl-14729820
ABSTRACT
Respiratory chain complex I deficiency represents a genetically heterogeneous group of diseases resulting from mutations in mitochondrial or nuclear genes. Mutations have been reported in 13 of the 14 subunits encoding the core of complex I (seven mitochondrial and six nuclear genes) and these result in Leigh or Leigh-like syndromes or cardiomyopathy. In this study, a combination of denaturing high performance liquid chromatography and sequence analysis was used to study the NDUFS3 gene in a series of complex I deficient patients. Mutations found in this gene (NADH dehydrogenase iron-sulphur protein 3), coding for the seventh and last subunit of complex I core, were shown to cause late onset Leigh syndrome, optic atrophy, and complex I deficiency. A biochemical diagnosis of complex I deficiency on cultured amniocytes from a later pregnancy was confirmed through the identification of disease causing NDUFS3 mutations in these cells. While mutations in the NDUFS3 gene thus result in Leigh syndrome, a dissimilar clinical phenotype is observed in mutations in the NDUFV2 and NDUFS2 genes, resulting in encephalomyopathy and cardiomyopathy. The reasons for these differences are uncertain.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Leigh
/
Subunidades de Proteína
/
Complejo I de Transporte de Electrón
/
Mutación
/
NADH Deshidrogenasa
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Child
/
Humans
/
Male
Idioma:
En
Revista:
J Med Genet
Año:
2004
Tipo del documento:
Article
País de afiliación:
Francia