Whole-mitochondrial genome sequencing in primary open-angle glaucoma using massively parallel sequencing identifies novel and known pathogenic variants

Periasamy Sundaresan, David A. Simpson, Chitra Sambare, Seamus Duffy, Judith Lechner, Aditi Dastane, Edward W. Dervan, Neeru Vallabh, Vidya Chelerkar, Madan Deshpande, Colm O'Brien, Amy Jayne McKnight, Colin Willoughby

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    PURPOSE:The aim of this study was to determine whether mutations in mitochondrial DNA play a role in high-pressure primary open-angle glaucoma (OMIM 137760) by analyzing new data from massively parallel sequencing of mitochondrial DNA.METHODS:Glaucoma patients with high-tension primary open-angle glaucoma and ethnically matched and age-matched control subjects without glaucoma were recruited. The entire human mitochondrial genome was amplified in two overlapping fragments by long-range polymerase chain reaction and used as a template for massively parallel sequencing on an Ion Torrent Personal Genome Machine. All variants were confirmed by conventional Sanger sequencing.RESULTS:Whole-mitochondrial genome sequencing was performed in 32 patients with primary open-angle glaucoma from India (n = 16) and Ireland (n = 16). In 16 of the 32 patients with primary open-angle glaucoma (50% of cases), there were 22 mitochondrial DNA mutations consisting of 7 novel mutations and 8 previously reported disease-associated sequence variants. Eight of 22 (36.4%) of the mitochondrial DNA mutations were in complex I mitochondrial genes.CONCLUSION:Massively parallel sequencing using the Ion Torrent Personal Genome Machine with confirmation by Sanger sequencing detected a pathogenic mitochondrial DNA mutation in 50% of the primary open-angle glaucoma cohort. Our findings support the emerging concept that mitochondrial dysfunction results in the development of glaucoma and, more specifically, that complex I defects play a significant role in primary open-angle glaucoma pathogenesis.
    Original languageEnglish
    Pages (from-to)279-284
    Number of pages5
    JournalGenetics in Medicine
    Issue number4
    Publication statusAccepted/In press - 7 Aug 2014



    • Genetics
    • Glaucoma
    • Mitochondrial genome
    • Next-generation sequencing

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