NDUFA2 complex I mutation leads to Leigh disease.
until further notice
SourceAmerican Journal of Human Genetics, 82, 6, (2008), pp. 1306-1315
Article / Letter to editor
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American Journal of Human Genetics
SubjectIGMD 3: Genomic disorders and inherited multi-system disorders; IGMD 8: Mitochondrial medicine; NCMLS 2: Metabolism, transport and motion; NCMLS 4: Energy and redox metabolism; ONCOL 3: Translational research; UMCN 5.3: Cellular energy metabolism; UMCN 5.4: Renal disorders
Mitochondrial isolated complex I deficiency is the most frequently encountered OXPHOS defect. We report a patient with an isolated complex I deficiency expressed in skin fibroblasts as well as muscle tissue. Because the parents were consanguineous, we performed homozygosity mapping to identify homozygous regions containing candidate genes such as NDUFA2 on chromosome 5. Screening of this gene on genomic DNA revealed a mutation that interferes with correct splicing and results in the skipping of exon 2. Exon skipping was confirmed on the mRNA level. The mutation in this accessory subunit causes reduced activity and disturbed assembly of complex I. Furthermore, the mutation is associated with a mitochondrial depolarization. The expression and activity of complex I and the depolarization was (partially) rescued with a baculovirus system expressing the NDUFA2 gene.
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