LHON/MELAS overlap syndrome associated with a mitochondrial MTND1 gene mutation

Blakely, Emma L.; Silva, Rajith de; King, Andrew; Schwarzer, Verena; Harrower, Tim; Dawidek, Gervase; Turnbull, Douglass M.; Taylor, Robert W.

doi:10.1038/sj.ejhg.5201363

Cited by 83 publications

(33 citation statements)

References 17 publications

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“…For instance, LHON/MELAS (Pulkes et al 1999), MELAS/MERRF (Naini et al 2005), and even Leigh/MELAS (Crimi et al 2003) overlap syndromes, all associated with ND5 mutations, have been reported (DiMauro and Hirano 2005). LHON/MELAS overlap syndrome associated with mutations in ND1 has also been reported (Blakely et al 2005).…”

Section: Clinical Manifestation and Genetic Heterogeneitymentioning

confidence: 99%

Mitochondrial complex I: Structure, function and pathology

Janßen

Nijtmans

Heuvel

et al. 2006

J of Inher Metab Disea

254

192

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Oxidative phosphorylation (OXPHOS) has a prominent role in energy metabolism of the cell. Being under bigenomic control, correct biogenesis and functioning of the OXPHOS system is dependent on the finely tuned interaction between the nuclear and the mitochondrial genome. This suggests that disturbances of the system can be caused by numerous genetic defects and can result in a variety of metabolic and biochemical alterations. Consequently, OXPHOS deficiencies manifest as a broad clinical spectrum. Complex I, the biggest and most complicated enzyme complex of the OXPHOS system, has been subjected to thorough investigation in recent years. Significant progress has been made in the field of structure, composition, assembly, and pathology. Important gains in the understanding of the Goliath of the OXPHOS system are: exposing the electron transfer mechanism and solving the crystal structure of the peripheral arm, characterization of almost all subunits and some of their functions, and creating models to elucidate the assembly process with concomitant identification of assembly chaperones. Unravelling the intricate mechanisms underlying the functioning of this membrane-bound enzyme complex in health and disease will pave the way for developing adequate diagnostic procedures and advanced therapeutic treatment strategies.

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Section: Clinical Manifestation and Genetic Heterogeneitymentioning

confidence: 99%

Mitochondrial complex I: Structure, function and pathology

Janßen

Nijtmans

Heuvel

et al. 2006

J of Inher Metab Disea

254

192

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“…47,48 Mt-co1 encodes a cytochrome C oxidase subunit. 49 Mt-cytb or mitochondriaencoded cytochrome B is also known as the bc1 complex or ubiquinol-cytochrome C reductase.…”

Section: Discussionmentioning

confidence: 99%

Rejuvenation of Cardiac Tissue Developed from Reprogrammed Aged Somatic Cells

Cheng

Peng

Zhang

et al. 2017

Rejuvenation Research

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Induced pluripotent stem cells (iPSCs) derived via somatic cell reprogramming have been reported to reset aged somatic cells to a more youthful state, characterized by elongated telomeres, a rearranged mitochondrial network, reduced oxidative stress, and restored pluripotency. However, it is still unclear whether the reprogrammed aged somatic cells can function normally as embryonic stem cells (ESCs) during development and be rejuvenated. In the current study, we applied the aggregation technique to investigate whether iPSCs derived from aged somatic cells could develop normally and be rejuvenated. iPSCs derived from bone marrow myeloid cells of 2-month-old (2 M) and 18-month-old (18 M) C57BL/6-Tg (CAG-EGFP)1Osb/J mice were aggregated with embryos derived from wild-type ICR mice to produce chimeras (referred to as 2 M CA and 18 M CA, respectively). Our observations focused on comparing the ability of the iPSCs derived from 18 M and 2 M bone marrow cells to develop rejuvenated cardiac tissue (the heart is the most vital organ during aging). The results showed an absence of p16 and p53 upregulation, telomere length shortening, and mitochondrial gene expression and deletion in 18 M CA, whereas slight changes in mitochondrial ultrastructure, cytochrome C oxidase activity, ATP production, and reactive oxygen species production were observed in CA cardiac tissues. The data implied that all of the aging characteristics observed in the newborn cardiac tissue of 18 M CA were comparable with those of 2 M CA newborn cardiac tissue. This study provides the first direct evidence of the aging-related characteristics of cardiac tissue developed from aged iPSCs, and our observations demonstrate that partial rejuvenation can be achieved by reprogramming aged somatic cells to a pluripotent state.

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“…33 Only two cases in the PubMed and OVID databases were reported as LHON/MELAS overlap syndrome. 3,6 They had typical clinical features of MELAS plus bilateral optic atrophy. G3376A and G13513A mutations, which encode for ND1 and ND5 subunits of Complex I, were harbored by these two cases, respectively.…”

Section: Ophthalmic Geneticsmentioning

confidence: 99%