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Background: Autosomal dominant optic atrophy (ADOA) is the commonest form of i nherited optic neuropathy. Mutations in the OPA1 gene encoding a dynamin-relate d mitochondrial protein underlie ADOA and may perturb the biogenesis and mainten ance of mitochondria. Objective: To investigate the mutation spectrum of the OPA 1 gene and assess alterations in mitochondrial content caused by OPA1 mutations. Methods:Sixteen Korean patients with clinically suspected ADOA were studied. Th e mutation spectrum of the OPA1 gene was analyzed by PCR single-strand conforma tion polymorphism and sequencing, and mitochondrial DNA (mtDNA) content was quan tified by real-time PCR. Results: Eight different mutations were found, includi ng five novel mutations. Quantitative real-time PCR analysis showed excellent l inearity and precision for the determination of mtDNA copy numbers. The number o f mtDNA copies per cell in patients with OPA1 gene mutations(ages 7 to 40) was s ignificantly lower than those in all normal control subjects (p=0.037), particul arly lower than in normalcontrol subjects ages 10 to 39 (p=0.022). Conclusion: T he mutation spectrum of the OPA1 gene disclosed marked genetic heterogeneity and the mitochondrial DNA content was found to be lower in autosomal dominant optic neuropathy, which provides direct evidence for a pathogenetic role of mutations of the OPA1 gene.
Background: Autosomal dominant optic atrophy (ADOA) is the commonest form of i nherited optic neuropathy. Mutations in the OPA1 gene encoding a dynamin-relate d mitochondrial protein underlie ADOA and may perturb the biogenesis and main ance of mitochondria. Objective: To investigate the mutation spectrum of the OPA1 gene and assess alterations in mitochondrial content caused by OPA1 mutations. Methods: Sixteen Korean patients with clinically suspected ADOA were studied. Th e mutation spectrum of the OPA1 gene was analyzed by PCR single-strand conformation polymorphism and sequencing , and mitochondrial DNA (mtDNA) content was quan tified by real-time PCR. Results: Eight different mutations were found, includi ng five novel mutations. Quantitative real-time PCR analysis showed excellent l inearity and precision for the determination of mtDNA copy numbers . The number of mtDNA copies per cell in patients with OPA1 gene mutations (ages 7 to 40) was s ignificantly lower than those in al Conclusion: T he mutation spectrum of the OPA1 gene revealed marked genetic heterogeneity and the mitochondrial DNA content was found to be (p = 0.037) lower in autosomal dominant optic neuropathy, which provides direct evidence for a pathogenetic role of mutations of the OPA1 gene.