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- Title
Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency.
- Authors
Haack, Tobias B; Danhauser, Katharina; Haberberger, Birgit; Hoser, Jonathan; Strecker, Valentina; Boehm, Detlef; Uziel, Graziella; Lamantea, Eleonora; Invernizzi, Federica; Poulton, Joanna; Rolinski, Boris; Iuso, Arcangela; Biskup, Saskia; Schmidt, Thorsten; Mewes, Hans-Werner; Wittig, Ilka; Meitinger, Thomas; Zeviani, Massimo; Prokisch, Holger
- Abstract
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.
- Publication
Nature genetics, 2010, Vol 42, Issue 12, p1131
- ISSN
1546-1718
- Publication type
Journal Article
- DOI
10.1038/ng.706