Cited by 54Mitochondrial Function and PathologyHereditary Neurological DisordersGlaucoma and retinal disorders

Mitochondrial variants may influence the phenotypic manifestation of Leber's hereditary optic neuropathy-associated ND4 G11778A mutation

Cai, Wanshi, Fu, Qun, Zhou, Xiangtian, Qu, Jia, Tong, Yi, Guan, Min-Xin·2008·Journal of Genetics and Genomics

Abstract

We report here the characterization of a five-generation Han Chinese family with Leber's hereditary optic neuropathy (LHON). Strikingly, this Chinese family displayed high penetrance and expressivity of visual loss. The average age-of-onset of vision loss was 18 years in this family. Nineteen (11 males/8 females) of 29 matrilineal relatives in this family developed visual loss with a wide range of severity, ranging from blindness to normal vision. Sequence analysis of mitochondrial genome in this pedigree revealed the presence of the ND4 G11778A mutation and 44 other variants belonging to Asian haplogroup M7b. The G11778A mutation is present at homoplasmy in matrilineal relatives of this Chinese family. Of other variants, the CO1 G6480A, ND5 T12811C and Cytb A15395G located at highly conserved residues of corresponding polypeptides. In fact, these variants were implicated to be involved in other clinical abnormalities. Here, these variants may act in synergy with the primary LHON-associated G11778A mutation. Thus, the mitochondrial dysfunction caused by the primary ND4 G11778A mutation may be worsened by these mitochondrial variants. The results imply that the G6480A, T12811C and A15395G variants might have a potential modifier role in increasing the penetrance and expressivity of the primary LHON-associated G11778A mutation in this Chinese family.

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Crossref · 10.1016/s1673-8527(08)60086-7

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  • Certain nucleotide changes that are not pathogenic per se may modulate the effects of deleterious mtDNA mutations.

    “Also, it has been frequently recognised that certain nucleotide changes that are not pathogenic per se may modulate the effects of deleterious mtDNA mutations [84,85].”

    From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [85]

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Authors
Cai, W., Fu, Q., Zhou, X., Qu, J., Tong, Y., & Guan, M.-X.
Affiliations
  • Wenzhou Medical University (CN)
  • Henan Medical University (CN)
  • Fujian Medical University (CN)
  • Cincinnati Children's Hospital Medical Center (US)
Corresponding author
Guan, Min-Xin
Venue
Journal of Genetics and Genomics
Publisher
Elsevier BV
Published
2008-11
Volume
35
Issue
11
Pages
649-655
ISSN
  • 1873-5533 (ISSN-L)
  • 1673-8527
OpenAlex
W2052339493
Cited by
54
References
27
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 4 · 2020: 3 · 2018: 7 · 2017: 4 · 2016: 4 · 2015: 2 · 2014: 1 · 2013: 5 · 2012: 9
FWCI
1.23
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of genetics and genomics/Journal of Genetics and Genomics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
  • Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
Keywords
Leber's hereditary optic neuropathy, mitochondrial DNA variants, homoplasmy, effect modification, penetrance, expressivity, vision loss, mitochondrial dysfunction, Han Chinese family
MeSH terms
Adolescent, Adult, Base Sequence, Child, China, DNA Mutational Analysis, DNA, Mitochondrial, Ethnicity, Female, Humans, Male, Mitochondria, Mutation, NADH Dehydrogenase, Pedigree, Phenotype, Optic Atrophy, Hereditary, Leber

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