Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency.

摘要: An isolated defect of respiratory chain complex I activity is a frequent biochemical abnormality in mitochondrial disorders. Despite intensive investigation recent years, most instances, the molecular basis underpinning defects remains unknown. We report whole-exome sequencing single individual with severe, deficiency. This analysis, followed by filtering prioritization proteins, led us to identify compound heterozygous mutations ACAD9, which encodes poorly understood member acyl-CoA dehydrogenase protein family. demonstrated pathogenic role ACAD9 variants correction on expression wildtype fibroblasts derived from affected individuals. screening 120 additional I-defective index cases two unrelated and total five alleles.