Academic Journal
Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency.
| العنوان: | Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency. |
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| المؤلفون: | Haack, T, Danhauser, K, Haberberger, B, Hoser, J, Strecker, V, Boehm, D, Uziel, G, Lamantea, E, Invernizzi, F, Poulton, J, Rolinski, B, Iuso, A, Biskup, S, Schmidt, T, Mewes, H, Wittig, I, Meitinger, T, Zeviani, M, Prokisch, H |
| سنة النشر: | 2016 |
| المجموعة: | Oxford University Research Archive (ORA) |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | https://ora.ox.ac.uk/objects/uuid:03fdd482-6107-48b8-888b-c999ac96f82e; https://doi.org/10.1038/ng.706 |
| DOI: | 10.1038/ng.706 |
| الاتاحة: | https://doi.org/10.1038/ng.706 https://ora.ox.ac.uk/objects/uuid:03fdd482-6107-48b8-888b-c999ac96f82e |
| Rights: | info:eu-repo/semantics/embargoedAccess |
| رقم الانضمام: | edsbas.FF34BF07 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/ng.706 |
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