High Mitochondrial DNA Copy Number Is a Protective Factor From Vision Loss in Heteroplasmic Leber's Hereditary Optic Neuropathy (LHON)
Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease that typically causes bilateral blindness in young men. It is characterized by as yet undisclosed genetic and environmental factors affecting the incomplete penetrance. We identified 27 LHON subjects who possess heteroplasmic...
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| Published in | Investigative ophthalmology & visual science Vol. 58; no. 4; p. 2193 |
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| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
01.04.2017
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1552-5783 0146-0404 1552-5783 |
| DOI | 10.1167/iovs.16-20389 |
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| Abstract | Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease that typically causes bilateral blindness in young men. It is characterized by as yet undisclosed genetic and environmental factors affecting the incomplete penetrance.
We identified 27 LHON subjects who possess heteroplasmic primary LHON mutations. Mitochondrial DNA (mtDNA) copy number was evaluated.
The presence of centrocecal scotoma, an edematous, hyperemic optic nerve head, and vascular tortuosity, as well as telangiectasia was recognized in affected subjects. We found higher cellular mtDNA content in peripheral blood cells of unaffected heteroplasmic mutation carriers with respect to the affected.
The increase of cellular mtDNA content prevents complete loss of vision despite the presence of a heteroplasmic state of LHON primary mutation, suggesting that it is a key factor responsible for penetrance of LHON. |
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| AbstractList | Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease that typically causes bilateral blindness in young men. It is characterized by as yet undisclosed genetic and environmental factors affecting the incomplete penetrance.
We identified 27 LHON subjects who possess heteroplasmic primary LHON mutations. Mitochondrial DNA (mtDNA) copy number was evaluated.
The presence of centrocecal scotoma, an edematous, hyperemic optic nerve head, and vascular tortuosity, as well as telangiectasia was recognized in affected subjects. We found higher cellular mtDNA content in peripheral blood cells of unaffected heteroplasmic mutation carriers with respect to the affected.
The increase of cellular mtDNA content prevents complete loss of vision despite the presence of a heteroplasmic state of LHON primary mutation, suggesting that it is a key factor responsible for penetrance of LHON. Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease that typically causes bilateral blindness in young men. It is characterized by as yet undisclosed genetic and environmental factors affecting the incomplete penetrance.PURPOSELeber's hereditary optic neuropathy (LHON) is a mitochondrial disease that typically causes bilateral blindness in young men. It is characterized by as yet undisclosed genetic and environmental factors affecting the incomplete penetrance.We identified 27 LHON subjects who possess heteroplasmic primary LHON mutations. Mitochondrial DNA (mtDNA) copy number was evaluated.METHODSWe identified 27 LHON subjects who possess heteroplasmic primary LHON mutations. Mitochondrial DNA (mtDNA) copy number was evaluated.The presence of centrocecal scotoma, an edematous, hyperemic optic nerve head, and vascular tortuosity, as well as telangiectasia was recognized in affected subjects. We found higher cellular mtDNA content in peripheral blood cells of unaffected heteroplasmic mutation carriers with respect to the affected.RESULTSThe presence of centrocecal scotoma, an edematous, hyperemic optic nerve head, and vascular tortuosity, as well as telangiectasia was recognized in affected subjects. We found higher cellular mtDNA content in peripheral blood cells of unaffected heteroplasmic mutation carriers with respect to the affected.The increase of cellular mtDNA content prevents complete loss of vision despite the presence of a heteroplasmic state of LHON primary mutation, suggesting that it is a key factor responsible for penetrance of LHON.CONCLUSIONSThe increase of cellular mtDNA content prevents complete loss of vision despite the presence of a heteroplasmic state of LHON primary mutation, suggesting that it is a key factor responsible for penetrance of LHON. |
| Author | Bisceglia, Luigi Montoya, Julio Bianco, Angelica Petruzzella, Vittoria Emperador, Sonia Guerriero, Silvana Palese, Luigi L. D'Agruma, Leonardo Russo, Luciana |
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| References | 28820924 - Invest Ophthalmol Vis Sci. 2017 Aug 1;58(10 ):4077 29346492 - Invest Ophthalmol Vis Sci. 2018 Jan 1;59(1):331 28820923 - Invest Ophthalmol Vis Sci. 2017 Aug 1;58(10 ):4076 29346491 - Invest Ophthalmol Vis Sci. 2018 Jan 1;59(1):330 |
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| SubjectTerms | Antioxidants - therapeutic use Blindness - prevention & control DNA Copy Number Variations DNA, Mitochondrial - genetics Female Genes, Mitochondrial - genetics Humans Male Mitochondria - genetics Mitochondrial Diseases - diagnosis Mitochondrial Diseases - drug therapy Mitochondrial Diseases - genetics Mutation Optic Atrophy, Hereditary, Leber - diagnosis Optic Atrophy, Hereditary, Leber - drug therapy Optic Atrophy, Hereditary, Leber - genetics Pedigree Polymerase Chain Reaction Polymorphism, Restriction Fragment Length Ubiquinone - analogs & derivatives Ubiquinone - therapeutic use Visual Acuity |
| Title | High Mitochondrial DNA Copy Number Is a Protective Factor From Vision Loss in Heteroplasmic Leber's Hereditary Optic Neuropathy (LHON) |
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