Leigh Syndrome Associated With Mitochondrial Complex I Deficiency Due to a Novel Mutation in the NDUFS1 Gene

Arch Neurol. 2005 Apr;62(4):659-61. doi: 10.1001/archneur.62.4.659.

Abstract

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.

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

Patient: 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / metabolism*
  • Brain / pathology
  • Brain / physiopathology
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics
  • Electron Transport Complex I / deficiency*
  • Electron Transport Complex I / genetics*
  • Fatal Outcome
  • Female
  • Genetic Testing
  • Humans
  • Infant
  • Leigh Disease / genetics*
  • Leigh Disease / metabolism
  • Leigh Disease / physiopathology
  • Male
  • Mitochondria / enzymology
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Muscle, Skeletal / metabolism
  • Mutation / genetics*
  • NADH Dehydrogenase
  • Spain

Substances

  • DNA, Mitochondrial
  • NDUFS1 protein, human
  • NADH Dehydrogenase
  • Electron Transport Complex I