Journal Article

Deep sequencing unearths Nuclear mitochondrial Sequences under Leber's hereditary optic neuropathy-associated false heteroplasmic mitochondrial DNA variants

Vittoria Petruzzella, Rosalba Carrozzo, Claudia Calabrese, Rosa Dell'Aglio, Raffaella Trentadue, Roberta Piredda, Lucia Artuso, Teresa Rizza, Marzia Bianchi, Anna Maria Porcelli, Silvana Guerriero, Giuseppe Gasparre and Marcella Attimonelli

in Human Molecular Genetics

Volume 21, issue 17, pages 3753-3764
Published in print September 2012 | ISSN: 0964-6906
Published online May 2012 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/dds182
Deep sequencing unearths Nuclear mitochondrial Sequences under Leber's hereditary optic neuropathy-associated false heteroplasmic mitochondrial DNA variants

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Leber's hereditary optic neuropathy (LHON) is associated with mitochondrial DNA (mtDNA) ND mutations that are mostly homoplasmic. However, these mutations are not sufficient to explain the peculiar features of penetrance and the tissue-specific expression of the disease and are believed to be causative in association with unknown environmental or other genetic factors. Discerning between clear-cut pathogenetic variants, such as those that appear to be heteroplasmic, and less penetrant variants, such as the homoplasmic, remains a challenging issue that we have addressed here using next-generation sequencing approach. We set up a protocol to quantify MTND5 heteroplasmy levels in a family in which the proband manifests a LHON phenotype. Furthermore, to study this mtDNA haplotype, we applied the cybridization protocol. The results demonstrate that the mutations are mostly homoplasmic, whereas the suspected heteroplasmic feature of the observed mutations is due to the co-amplification of Nuclear mitochondrial Sequences.

Journal Article.  7462 words.  Illustrated.

Subjects: Genetics and Genomics

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