chipbased mtdna mutation screening enables fast and reliable genetic diagnosis of oxphos patients purpose oxidative phosphorylation is under dual genetic control of the nuclear and the mitochondrial dna mtdna oxidative phosphorylation disorders are clinically and genetically heterogeneous which makes it difficult to determine the genetic defect and symptombased protocols which link clinical symptoms directly to a specific gene or mtdna mutation are falling short moreover approximately 25 of the pediatric patients with oxidative phosphorylation disorders is estimated to have mutations in the mtdna and a standard screening approach for common mutations and deletions will only explain part of these cases therefore we tested a new chipbased screening method for the mtdnamethods mitochip affymetrix resequencing was performed on three test samples and on 28 patient samplesresults call rates were 94 on average and heteroplasmy detection levels varied from 550 a genetic diagnosis can be made in almost onequarter of the patients at a potential output of 8 complete mtdna sequences every 4 days moreover a number of potentially pathogenic unclassified variants uv were detectedconclusions the availability of longrange pcr protocols and the predominance of single nucleotide substitutions in the mtdna make the resequencing chip a very fast and reliable method to screen the complete mtdna for mutations