Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency.
Nat. Genet. 42, 1131-1134 (2010)
An isolated defect of respiratory chain complex I activity is a frequent biochemical abnormality in mitochondrial disorders. Despite intensive investigation in recent years, in most instances, the molecular basis underpinning complex I defects remains unknown. We report whole-exome sequencing of a single individual with severe, isolated complex I deficiency. This analysis, followed by filtering with a prioritization of mitochondrial proteins, led us to identify compound heterozygous mutations in ACAD9, which encodes a poorly understood member of the mitochondrial acyl-CoA dehydrogenase protein family. We demonstrated the pathogenic role of the ACAD9 variants by the correction of the complex I defect on expression of the wildtype ACAD9 protein in fibroblasts derived from affected individuals. ACAD9 screening of 120 additional complex I-defective index cases led us to identify two additional unrelated cases and a total of five pathogenic ACAD9 alleles.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter beta-oxidation; mitochondrial; diagnosis; database; capture; cells; page
ISSN (print) / ISBN 1061-4036
Zeitschrift Nature Genetics
Quellenangaben Band: 42, Heft: 12, Seiten: 1131-1134
Verlag Nature America
Verlagsort New York, NY