MELAS Syndrome with Cardiac Involvement: A Multimodality Imaging Approach

Seitun, Sara; Massobrio, Laura; Rubegni, Anna; Nesti, Claudia; Morelli, Margherita Castiglione; Boccalini, Sara; Pregliasco, Athena Galletto; Budaj, Irilda; Deferrari, Luca; Rosa, Gian Marco; Montecucco, Fabrizio; Valbusa, Alberto

doi:10.1155/2016/1490181

Cited by 7 publications

(8 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In recent years, MELAS has been reported to associate with the development of atherosclerotic lesions and cardiovascular diseases 10,31 . While the primary cause of SLEs in MELAS patients remains controversial, factors such as mitochondrial cytopathy, mitochondrial angiopathy and non-ischaemic neurovascular cellular mechanism, or combined, have been regarded as key contributing factors to disease onset and progression 32 .…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial 3243A > G mutation confers pro-atherogenic and pro-inflammatory properties in MELAS iPS derived endothelial cells

Pek

Phua

et al. 2019

Cell Death Dis

View full text Add to dashboard Cite

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder that is commonly caused by the m.3243A > G mutation in the MT-TL1 gene encoding for mitochondrial tRNA(Leu(UUR)). While clinical studies reported cerebral infarcts, atherosclerotic lesions, and altered vasculature and stroke-like episodes (SLE) in MELAS patients, it remains unclear how this mutation causes the onset and subsequent progression of the disease. Here, we report that in addition to endothelial dysfunction, diseased endothelial cells (ECs) were found to be pro-atherogenic and pro-inflammation due to high levels of ROS and Ox-LDLs, and high basal expressions of VCAM-1, in particular isoform b, respectively. Consistently, more monocytes were found to adhere to MELAS ECs as compared to the isogenic control, suggesting the presence of an atherosclerosis-like pathology in MELAS. Notably, these disease phenotypes in endothelial cells can be effectively reversed by anti-oxidant treatment suggesting that the lowering of ROS is critical for treating patients with MELAS syndrome.

show abstract

Section: Discussionmentioning

confidence: 99%

Mitochondrial 3243A > G mutation confers pro-atherogenic and pro-inflammatory properties in MELAS iPS derived endothelial cells

Pek

Phua

et al. 2019

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…Previous studies have reported many mitochondrial mutations causing classic MELAS without any detectable phenotypic specificity [88,89]; exceptional renal diseases were detected in association with m.3243 and m.13513G>A as a first manifestation of MELAS [90,91]. Furthermore, MELAS m.3243 was associated with uncommon presentations such as cardiac and ketoacidosis [92,93].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

“…1 Several other MELAS patients with a PFO have been reported. 6 For example, PFO has been reported in a 41 year-old male with MELAS due to the variant m.3243A > G in MT-TL1. 6 No mention is made of what treatment the patient received for the three "ischemic" strokes.…”

Section: Stroke-like Lesions Should Not Be Mixed Up With Ischemic Str...mentioning

confidence: 99%

“…6 For example, PFO has been reported in a 41 year-old male with MELAS due to the variant m.3243A > G in MT-TL1. 6 No mention is made of what treatment the patient received for the three "ischemic" strokes. Has he ever had thrombolysis or thrombectomy?…”

Section: Stroke-like Lesions Should Not Be Mixed Up With Ischemic Str...mentioning

confidence: 99%

Stroke‐like lesions should not be mixed up with ischemic stroke in MELAS with cardioembolic risk

Finsterer

2023

Clinical Case Reports

View full text Add to dashboard Cite

MELAS Syndrome with Cardiac Involvement: A Multimodality Imaging Approach

Cited by 7 publications

References 11 publications

Mitochondrial 3243A > G mutation confers pro-atherogenic and pro-inflammatory properties in MELAS iPS derived endothelial cells

Mitochondrial 3243A > G mutation confers pro-atherogenic and pro-inflammatory properties in MELAS iPS derived endothelial cells

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

Stroke‐like lesions should not be mixed up with ischemic stroke in MELAS with cardioembolic risk

Contact Info

Product

Resources

About