NDUFA2 complex I mutation leads to Leigh disease.
Am J Hum Genet
; 82(6): 1306-15, 2008 Jun.
Article
en En
| MEDLINE
| ID: mdl-18513682
ABSTRACT
Mitochondrial isolated complex I deficiency is the most frequently encountered OXPHOS defect. We report a patient with an isolated complex I deficiency expressed in skin fibroblasts as well as muscle tissue. Because the parents were consanguineous, we performed homozygosity mapping to identify homozygous regions containing candidate genes such as NDUFA2 on chromosome 5. Screening of this gene on genomic DNA revealed a mutation that interferes with correct splicing and results in the skipping of exon 2. Exon skipping was confirmed on the mRNA level. The mutation in this accessory subunit causes reduced activity and disturbed assembly of complex I. Furthermore, the mutation is associated with a mitochondrial depolarization. The expression and activity of complex I and the depolarization was (partially) rescued with a baculovirus system expressing the NDUFA2 gene.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Leigh
/
Complejo I de Transporte de Electrón
/
Mutación
Tipo de estudio:
Prognostic_studies
Límite:
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Am J Hum Genet
Año:
2008
Tipo del documento:
Article
País de afiliación:
Países Bajos