Increased mtDNA Copy Number Does Not Protect Against LHON

Finsterer, Josef; Zarrouk‐Mahjoub, Sinda

doi:10.1167/iovs.17-22640

Cited by 3 publications

(1 citation statement)

References 6 publications

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“…Therefore, high mtDNA copy number means that cell may provide sufficient amount of normal mitochondria to rescue the metabolic damage caused by mutant mtDNA. There is emerging evidence supporting high mtDNA copy number as the protective factor from LHON manifestation,7,31 although with some controversies 41,42. Clearly, to increase the cellular mtDNA content would be considered a promising therapeutic strategy for LHON, and a list of compounds have been recommended 43.…”

Section: Discussionmentioning

confidence: 99%

Leber's Hereditary Optic Neuropathy–Specific Heteroplasmic Mutation m.14495A>G Found in a Chinese Family

Duan

Qin

et al. 2019

Trans. Vis. Sci. Tech.

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Purpose Leber's hereditary optic neuropathy (LHON) is a mitochondrial DNA (mtDNA)-associated, maternally inherited eye disease. Mutation heteroplasmy level is one of the leading causes to trigger LHON manifestation. In this study, we aimed to identify the causative mutation in a large Han Chinese family with LHON and explore the underlying pathogenic mechanism in this LHON family. Methods The whole-mtDNA sequence was amplified by long-range PCR. Mutations were subsequently identified by next-generation sequencing (NGS) and validated by Sanger sequencing. The heteroplasmy rates of those family members were determined by digital PCR (dPCR). Mitochondrial haplogroups were assigned based on mtDNA tree build 17. Results The m.14495A>G mutation was identified as causative due to its higher heteroplasmy level (>50%) in patients than in their unaffected relatives. All mutation carriers belong to M7b1a1 and are assigned to Asian mtDNA lineage. Interestingly, our result revealed that high mtDNA copy number in carrier might prevent LHON manifestation. Conclusions This is the first report of m.14495A>G mutation in Asian individuals with LHON. Our study shows that dPCR technology can provide more reliable results in mutation heteroplasmy assay and determination of the cellular mtDNA content, making it a potentially promising tool for clinical precise diagnosis of LHON. Furthermore, our results also add evidence to the opinion that higher mtDNA content may protect mutation carriers from LHON. Translational Relevance dPCR can be used for the assessment of LHON disease, and a new genetic-based diagnostic strategy has been proposed for LHON patients with the m.14495A>G mutation.

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Section: Discussionmentioning

confidence: 99%

Leber's Hereditary Optic Neuropathy–Specific Heteroplasmic Mutation m.14495A>G Found in a Chinese Family

Duan

Qin

et al. 2019

Trans. Vis. Sci. Tech.

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Emerging model systems and treatment approaches for Leber's hereditary optic neuropathy: Challenges and opportunities

Bahr

Welburn

Donnelly

et al. 2020

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Author Response: Increased mtDNA Copy Number Protects Against LHON

Bianco

Palese

Guerriero

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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Increased mtDNA Copy Number Does Not Protect Against LHON

Cited by 3 publications

References 6 publications

Leber's Hereditary Optic Neuropathy–Specific Heteroplasmic Mutation m.14495A>G Found in a Chinese Family

Leber's Hereditary Optic Neuropathy–Specific Heteroplasmic Mutation m.14495A>G Found in a Chinese Family

Emerging model systems and treatment approaches for Leber's hereditary optic neuropathy: Challenges and opportunities

Author Response: Increased mtDNA Copy Number Protects Against LHON

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Increased mtDNA Copy Number Does Not Protect Against LHON

Cited by 3 publications

References 6 publications

Leber's Hereditary Optic Neuropathy–Specific Heteroplasmic Mutation m.14495A&gt;G Found in a Chinese Family

Leber's Hereditary Optic Neuropathy–Specific Heteroplasmic Mutation m.14495A&gt;G Found in a Chinese Family

Emerging model systems and treatment approaches for Leber's hereditary optic neuropathy: Challenges and opportunities

Author Response: Increased mtDNA Copy Number Protects Against LHON

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Leber's Hereditary Optic Neuropathy–Specific Heteroplasmic Mutation m.14495A>G Found in a Chinese Family

Leber's Hereditary Optic Neuropathy–Specific Heteroplasmic Mutation m.14495A>G Found in a Chinese Family