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Xia wang, Donna Muzny, Robert K. Koenekoop, Yuanqing Wu, Christian Buhay, Hui Wang, Irma Lopez, Min Wang, Richard A. Gibbs, Rui Chen; Clinical Diagnosis by Targeted Sequencing Using Personal Genome Machine. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4568.
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The molecular mechanisms for human genetic disorders are complex and the genetic heterogeneity is widely observed. Therefore, accurate molecular diagnosis of such genetic diseases, coupled with clinical phenotype, is the first step toward personalized treatment. The use of next generation sequencing (NGS) technology has the potential to dramatically improve molecular diagnostics. To introduce NGS to clinics, the sequencing method needs to be accurate, robust, rapid, and cost effective. The recently released Personal Genome Machine (PGM) is aiming to achieve these goals.The goal of this study is to test the efficacy and potential utility of PGM platform in a clinical setting.
Coupled with gene capture technology, genomic DNA from a well characterized hapmap sample as well as two patients with autosomal recessive retinitis pigmentosa (arRP) was sequenced on the PGM platform. Systematic evaluation of the data coverage and accuracy was performed using both SNP genotyping microarray as well as Sanger sequencing. Putative mutations were Sanger sequenced, tested for the segregation within families, and screened in controls.
High quality results have been obtained from the sequencing of a well characterized hapmap sample with 99.59% (1181/1185) overall accuracy. Compound heterozygous mutations have been identified for both patients in USH2A. The c.2276G>T missense mutation and c.2299delG deletion were previously reported in RP patients. c.457T>G is a novel missense mutation.
This study represents the first reported human patient case diagnosed by the PGM platform and demonstrates the potential utility of the PGM platform in a clinical setting.
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