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Leigh Syndrome Associated With Mitochondrial Complex I Deficiency Due to a Novel Mutation in the NDUFS1 Gene
Miguel A. Martín, PhD;
Alberto Blázquez, BSc;
Luis G. Gutierrez-Solana, MD;
Daniel Fernández-Moreira, PharmB;
Paz Briones, PhD;
Antoni L. Andreu, MD, PhD;
Rafael Garesse, PhD;
Yolanda Campos, PhD;
Joaquín Arenas, PhD
Arch Neurol. 2005;62:659-661.
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.
Author Affiliations: Centro de Investigación, Hospital Universitario 12 de Octubre (Drs Martín, Campos, and Arenas and Messrs Blázquez and Fernández-Moreira), Servicio de Neurología, Hospital Infantil Universitario Niño Jesús (Dr Gutierrez-Solana), Instituto Investigaciones Biomédicas "Alberto Sols" Universidad Autónoma de Madrid–Consejo Superior de Investigaciones Cientificas, Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid (Dr Garesse), Madrid; and Institut de Bioquímica Clínica, Corporació Sanitaria Clínic y Consejo Superior de Investigaciones Cientificas (Dr Briones) and Centre d’Investigacions en Bioquímica i Biología Molecular, Hospital Universitari Vall d’Hebron (Dr Andreu), Barcelona, Spain. Dr Martín and Mr Blázquez contributed equally to this work.
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