Leigh syndrome associated with mitochondrial complex I deficiency due to a novel mutation in the NDUFS1 gene.
BACKGROUND
Mutations in the nuclear-encoded subunits of complex I of the mitochondrial respiratory chain are a recognized cause of Leigh syndrome (LS). Recently, 6 mutations in the NDUFS1 gene were identified in 3 families.


OBJECTIVE
To describe a Spanish family with LS, complex I deficiency in muscle, and a novel mutation in the NDUFS1 gene.


METHODS
Using molecular genetic approaches, we identified the underlying molecular defect in a patient with LS with a complex I defect.


METHODS
The proband was a child who displayed the clinical features of LS.


RESULTS
Muscle biochemistry results showed a complex I defect of the mitochondrial respiratory chain. Sequencing analysis of the mitochondrial DNA-encoded ND genes, the nuclear DNA-encoded NDUFV1, NDUFS1, NDUFS2, NDUFS4, NDUFS6, NDUFS7, NDUFS8, and NDUFAB1 genes, and the complex I assembly factor CIA30 gene revealed a novel homozygous L231V mutation (c.691C-->G) in the NDUFS1 gene. The parents were heterozygous carriers of the L231V mutation.


CONCLUSIONS
Identifying nuclear mutations as a cause of respiratory chain disorders will enhance the possibility of prenatal diagnosis and help us understand how molecular defects can lead to complex I deficiency.
Martín
Miguel A
MA
Centro de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain.
Blázquez
Alberto
A
Gutierrez-Solana
Luis G
LG
Fernández-Moreira
Daniel
D
Briones
Paz
P
Andreu
Antoni L
AL
Garesse
Rafael
R
Campos
Yolanda
Y
Arenas
Joaquín
J
D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D042967:Electron Transport Complex I / Q000172:deficiency* / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009245:NADH Dehydrogenase; D013030:Spain
D004272:DNA, Mitochondrial; C487793:NDUFS1 protein, human; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I