Homozygosity mapping was performed in five patients from a consanguineous family who presented with infantile mitochondrial encephalomyopathy attributed to isolated NADH:ubiquinone oxidoreductase (complex I) deficiency. This resulted in the identification of a missense mutation in a conserved residue of the C6ORF66 gene, which encodes a 20.2 kDa mitochondrial protein. The mutation was also detected in a patient who presented with antenatal cardiomyopathy. In muscle of two patients, the levels of the C6ORF66 protein and of the fully assembled complex I were markedly reduced. Transfection of the patients' fibroblasts with wild-type C6ORF66 cDNA restored complex I activity. These data suggest that C6ORF66 is an assembly factor of complex I. Interestingly, the C6ORF66 gene product was previously shown to promote breast cancer cell invasiveness.
Bibliographical noteFunding Information:
We are grateful to Corinne Belaiche of the Metabolic Disease Unit, Hadassah Medical Center, and to Zohar Itzhaki of the Department of Molecular Genetics and Biotechnology, Faculty of Medicine, The Hebrew University, Jerusalem. This work was supported in part by the United Mitochondrial Disease Foundation (grant number 07-204B) and by the Joint Research Fund of the Hebrew University and Hadassah Medical Organization.