Mitochondrial haplogroup D4j specific variant m.11696G &gt; a(
            <i>MT-ND4</i>
            ) may increase the penetrance and expressivity of the LHON-associated m.11778G &gt; a mutation in Chinese pedigrees

Xie, Shipeng; Zhang, Juanjuan; Sun, Jiji; Zhang, Minglian; Zhao, Fuxin; Wei, Qi-Ping; Tong, Yi; Liu, Xiaoling; Zhou, Xiangtian; Jiang, Pingping; Ji, Yanchun; Guan, Min‐Xin

doi:10.3109/19401736.2015.1136304

Cited by 16 publications

(15 citation statements)

References 38 publications

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“…In these two families, the age of onset for visual impairment ranged between 6 and 32 years old (average, 20.5 years old). Previous studies confirmed that the age of onset for visual impairment in the two pedigrees harboring the m.5587T>C mutation was similar to that in other Chinese families with LHON carrying the m.11778G>A mutation (28)(29)(30)(31)(32). In contrast, a number of Chinese subjects carrying the m.11778G>A mutation, which exhibited profound visual loss, the affected subjects carrying the m.5587T>C mutation suffered from mild to profound visual impairment, similar to that exhibited in patients carrying m.3394T>C, m.3635G>A, m.3866T>C, m.11696G>A, m.12238T>C and m.14502T>C mutations (15)(16)(17)(18)(19)33).…”

Section: Discussionsupporting

confidence: 71%

Leber's hereditary optic neuropathy is potentially associated with a novel m.5587T>C mutation in two pedigrees

Qiao

Liang

et al. 2017

Molecular Medicine Reports

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Mitochondrial (mt)DNA mutations have been revealed to be associated with Leber's hereditary optic neuropathy (LHON). The present study conducted clinical, genetic and molecular evaluations of two Han Chinese families. A total of 4 (3 men and 1 female) out of 14 matrilineal relatives in the families exhibited visual impairment with variable severity and age of onset. The average age of onset of visual loss was 20.5 years old. Molecular analysis of the complete mitochondrial genome in these pedigrees demonstrated that the three primary mutations associated with LHON were not detected; however, the homoplasmic m.5587T>C mutation was identified, which was localized at the end of the mitochondrially encoded transfer (t)RNA alanine gene and may alter the tertiary structure of this tRNA. Subsequently, this structural alteration may result in tRNA metabolism failure. In addition, distinct sets of mtDNA polymorphisms belonging to haplogroup F1 were detected in both families tested. The findings of the present study suggested that the m.5587T>C mutation may be involved in the pathogenesis of visual impairment. In addition, the mtDNA variant m.15024G>A(p.C93H) in the mitochondrially encoded cytochrome B gene was detected in both families, which exhibited evolutionary conservation, indicating it may serve a potential modifying role in the development of visual impairment associated with m.5587T>C mutation in these families. Furthermore, other modifying factors, including nuclear modifier genes, and environmental and personal factors may also contribute to the development of LHON in subjects carrying this mutation.

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Section: Discussionsupporting

confidence: 71%

Leber's hereditary optic neuropathy is potentially associated with a novel m.5587T>C mutation in two pedigrees

Qiao

Liang

et al. 2017

Molecular Medicine Reports

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“…We further used an online application (http://www .mitotool.org/genomeRSRS.html) in order to determine the mitochondrial haplogroup of the proband and related individuals, consistent with current haplogroup nomenclature [17,18].…”

Section: Phylogenetic Analysesmentioning

confidence: 99%

Maternally Inherited Diabetes Mellitus Associated with a Novel m.15897G>A Mutation in Mitochondrial tRNA^Thr Gene

Liu

et al. 2020

Journal of Diabetes Research

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We report here the clinical, genetic, and molecular characteristics of type 2 diabetes in a Chinese family. There are differences in the severity and age of onset in diabetes among these families. By molecular analysis of the complete mitochondrial genome in this family, we identified the homoplasmic m.15897G>A mutation underwent sequence analysis of whole mitochondrial DNA genome, which localized at conventional position ten of tRNAThr, and distinct sets of mtDNA polymorphisms belonging to haplogroup D4b1. This mutation has been implicated to be important for tRNA identity and stability. Using cybrid cell models, the decreased efficiency of mitochondrial tRNAThr levels caused by the m.15897G>A mutation results in respiratory deficiency, protein synthesis and assembly, mitochondrial ATP synthesis, and mitochondrial membrane potential. These mitochondrial dysfunctions caused an increase in the production of reactive oxygen species in the mutant cell lines. These data provide a direct evidence that a novel tRNA mutation was associated with T2DM. Thus, our findings provide a new insight into the understanding of pathophysiology of maternally inherited diabetes.

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“…We further used an online application (www.mitotool.org/genomeRSRS.html) in order to determine the mitochondrial haplogroup of the proband and related individuals, consistent with current haplogroup nomenclature [17,18].…”

Section: Phylogenetic Analysesmentioning

confidence: 99%

Mutation at position 5628 in the mitochondrial tRNAAla gene in a Chinese pedigree with maternally diabetes mellitus

Li¹,

Wu²,

Lin³

et al. 2019

Preprint

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Background: To investigate the clinical, genetic and molecular characteristics of mitochondrial diabetes mellitus (MDM). Methods: Resultant variants were evaluated for evolutionary conservation, allelic frequencies, and structural and functional consequences. The mitochondrial function including mitochondrial tRNAAla levels, protein synthesis, membrane potential, adenosine triphosphate (ATP) production, and reactive oxygen species (ROS) generation were measured using lymphoblastoid cell lines carrying the m.5628T>C mutation and 2 controls .Results: We observed differences in the severity and age of onset in diabetes in affected maternally-related individuals, and through amolecular of the complete mitochondrial genome in this family, we identified a homoplasmic m.5628T>C mutation, located at conventional position 31 of tRNAAla, and we further detected distinct sets of mtDNA polymorphisms belonging to haplogroup L1. The identified mutation was further found be important for tRNA identity and stability. Using cellular models, we were able to determine that the respiratory deficiency caused arising as a consequence of the m.5628T>C mutation led to decreased efficiency of mitochondrial tRNAAla levels, protein synthesis, mitochondrial ATP synthesis and a reduced mitochondrial membrane potential.These mitochondrial dysfunctions caused an increase in the production of reactive oxygen species in the mutant cell lines. Conclusions: These data provide a direct evidence that novel m.5628T>C mutation may be associated with MDM, thus, offering novel insights into the understanding of pathophysiology of MDM.

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Mitochondrial haplogroup D4j specific variant m.11696G > a( MT-ND4 ) may increase the penetrance and expressivity of the LHON-associated m.11778G > a mutation in Chinese pedigrees

Cited by 16 publications

References 38 publications

Leber's hereditary optic neuropathy is potentially associated with a novel m.5587T>C mutation in two pedigrees

Leber's hereditary optic neuropathy is potentially associated with a novel m.5587T>C mutation in two pedigrees

Maternally Inherited Diabetes Mellitus Associated with a Novel m.15897G>A Mutation in Mitochondrial tRNA^Thr Gene

Mutation at position 5628 in the mitochondrial tRNAAla gene in a Chinese pedigree with maternally diabetes mellitus

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Mitochondrial haplogroup D4j specific variant m.11696G > a( MT-ND4 ) may increase the penetrance and expressivity of the LHON-associated m.11778G > a mutation in Chinese pedigrees

Cited by 16 publications

References 38 publications

Leber's hereditary optic neuropathy is potentially associated with a novel m.5587T>C mutation in two pedigrees

Leber's hereditary optic neuropathy is potentially associated with a novel m.5587T>C mutation in two pedigrees

Maternally Inherited Diabetes Mellitus Associated with a Novel m.15897G>A Mutation in Mitochondrial tRNAThr Gene

Mutation at position 5628 in the mitochondrial tRNAAla gene in a Chinese pedigree with maternally diabetes mellitus

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Maternally Inherited Diabetes Mellitus Associated with a Novel m.15897G>A Mutation in Mitochondrial tRNA^Thr Gene