This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (5)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Neurogenetics  • Alert me on articles by topic  Social Bookmarking   What's this?

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.691CG) 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.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Mitochondrial complex I deficiency: from organelle dysfunction to clinical disease
Distelmaier et al.
Brain 2009;132:833-842.
ABSTRACT | FULL TEXT  

A novel deletion in the GTPase domain of OPA1 causes defects in mitochondrial morphology and distribution, but not in function
Spinazzi et al.
Hum Mol Genet 2008;17:3291-3302.
ABSTRACT | FULL TEXT  

Natural variation and genetic covariance in adult hippocampal neurogenesis
Kempermann et al.
Proc. Natl. Acad. Sci. USA 2006;103:780-785.
ABSTRACT | FULL TEXT