Mitochondrial Medicine: A Historical Point of View

Ng, Yi Shiau; DiMauro, Salvatore; Turnbull, D.M.

doi:10.1007/978-3-030-05517-2_1

Cited by 2 publications

(2 citation statements)

References 134 publications

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“…Disorders of mitochondrial encephalomyopathies are the most frequent group of inherited neurogenetic disorders, caused by point mutations in mtDNA that disrupt the formation of mitochondrially encoded respiratory chain subunits and therefore cause respiratory chain dysfunction. MEMP mainly presented clinically by different phenotypes [55][56][57]. By direct Sanger sequencing of mtDNA in this study, our genetic analysis reported the first sporadic case of mtDNA-associated Leigh syndrome disclosed in a four year old Serbian girl (P3) who was diagnosed according to the criteria declared by Rahman et al for a neurodegenerative disease with psychomotor developmental retardation, sluggishness of the motor system, muscle weakness, sever epileptic attacks, nystagmus, dystonia and regression in infancy as a results of basal ganglia and/or brainstem damage accompanied by the characteristic features of hyperintense lesions on T2-weighted on MRI and biochemical lactosidosis [58,59].…”

Section: Discussionmentioning

confidence: 99%

Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review

et al. 2021

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Mitochondrial encephalomyopathies (MEMP) are heterogeneous multisystem disorders frequently associated with mitochondrial DNA (mtDNA) mutations. Clinical presentation varies considerably in age of onset, course, and severity up to death in early childhood. In this study, we performed molecular genetic analysis for mtDNA pathogenic mutation detection in Serbian children, preliminary diagnosed clinically, biochemically and by brain imaging for mitochondrial encephalomyopathies disorders. Sanger sequencing analysis in three Serbian probands revealed two known pathogenic mutations. Two probands had a heteroplasmic point mutation m.3243A>G in the MT-TL1 gene, which confirmed mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode syndrome (MELAS), while a single case clinically manifested for Leigh syndrome had an almost homoplasmic (close to 100%) m.8993T>G mutation in the MT-ATP6 gene. After full mtDNA MITOMASTER analysis and PhyloTree build 17, we report MELAS’ association with haplogroups U and H (U2e and H15 subclades); likewise, the mtDNA-associated Leigh syndrome proband shows a preference for haplogroup H (H34 subclade). Based on clinical–genetic correlation, we suggest that haplogroup H may contribute to the mitochondrial encephalomyopathies’ phenotypic variability of the patients in our study. We conclude that genetic studies for the distinctive mitochondrial encephalomyopathies should be well-considered for realizing clinical severity and possible outcomes.

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Section: Discussionmentioning

confidence: 99%

Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review

et al. 2021

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“…A unique classical expression of this disease is the appearance of RRFs in skeletal muscle biopsies. Several other less common symptoms including peripheral neuropathy and dementia have also been exhibited [60,63,64]. Usually, young adults are affected by "NARP" and retinitis pigmentosa, sensory neuropathy, proximal weakness, etc.…”

Section: Clinical Features and Burden Of Mitochondrial Disordersmentioning

confidence: 99%

Use of Next-Generation Sequencing for Identifying Mitochondrial Disorders

Mahmud

Biswas

Afrose

et al. 2022

CIMB

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Mitochondria are major contributors to ATP synthesis, generating more than 90% of the total cellular energy production through oxidative phosphorylation (OXPHOS): metabolite oxidation, such as the β-oxidation of fatty acids, and the Krebs’s cycle. OXPHOS inadequacy due to large genetic lesions in mitochondrial as well as nuclear genes and homo- or heteroplasmic point mutations in mitochondrially encoded genes is a characteristic of heterogeneous, maternally inherited genetic disorders known as mitochondrial disorders that affect multisystemic tissues and organs with high energy requirements, resulting in various signs and symptoms. Several traditional diagnostic approaches, including magnetic resonance imaging of the brain, cardiac testing, biochemical screening, variable heteroplasmy genetic testing, identifying clinical features, and skeletal muscle biopsies, are associated with increased risks, high costs, a high degree of false-positive or false-negative results, or a lack of precision, which limits their diagnostic abilities for mitochondrial disorders. Variable heteroplasmy levels, mtDNA depletion, and the identification of pathogenic variants can be detected through genetic sequencing, including the gold standard Sanger sequencing. However, sequencing can be time consuming, and Sanger sequencing can result in the missed recognition of larger structural variations such as CNVs or copy-number variations. Although each sequencing method has its own limitations, genetic sequencing can be an alternative to traditional diagnostic methods. The ever-growing roster of possible mutations has led to the development of next-generation sequencing (NGS). The enhancement of NGS methods can offer a precise diagnosis of the mitochondrial disorder within a short period at a reasonable expense for both research and clinical applications.

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Mitochondrial Medicine: A Historical Point of View

Cited by 2 publications

References 134 publications

Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review

Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review

Use of Next-Generation Sequencing for Identifying Mitochondrial Disorders

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