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

Dawod, Phepy G A; Jančić, Jasna; Marjanovic, Ana; Branković, Miloš; Janković, Milena; Samardžić, Janko; Dawod, Ayman G. A.; Novaković, Ivana; Motaleb, Fayda Ibrahim Abdel; Radlovic, Vladimir; Kostić, Vladimir; Nikolić, Dejan

doi:10.3390/diagnostics11111969

Cited by 2 publications

(4 citation statements)

References 114 publications

(119 reference statements)

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“…We can first screen for hot spot gene mutations in Chinese MELAS syndrome patients such as mtDNA3243A>G, mtDNA13513G>A and mtDNA3271T>C, or perform full-length mtDNA sequencing and/or related nuclear gene detection[ 13 ]. The mutated gene in most patients with MELAS syndrome is mtDNA3243A>G[ 2 , 5 ]. The region where the mtDNA3243A locus is located encodes a transfer RNA.…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondrial encephalomyopathy (ME) is a multisystem metabolic disorder mainly caused by mutations in mitochondrial DNA (mtDNA) or nuclear DNA, resulting in abnormal mitochondrial structure and function and insufficient ATP synthesis[ 1 , 2 ]. ME has six main subtypes: ME, lactic acidosis, and stroke-like episode (MELAS) syndrome; Leigh syndrome (LS); Leber’s hereditary optic neuropathy; chronic progressive external ophthalmoplegia (CPEO); myoclonus epilepsy with ragged-red fiber (MERRF); and Keams-sayre syndrome.…”

Section: Introductionmentioning

confidence: 99%

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Familial mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome: Three case reports

Xiao¹,

Fu²

2022

WJCC

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BACKGROUND Mitochondrial encephalomyopathy (ME) is a multisystem metabolic disease that primarily affects the central nervous system and skeletal muscle. It is caused by mutations in mitochondrial or nuclear DNA, resulting in abnormal mitochondrial structure and function and insufficient ATP synthesis. The most common subtype is mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome. In recent years, reports of MELAS syndrome have increased but familial cases are rare. CASE SUMMARY We report a case of familial MELAS syndrome. Cases 2 and 3 are sisters and case 1 is their nephew. All are short in stature and showed stroke-like episodes with rapid onset and no obvious symptoms such as paroxysmal headache, aphasia, or blurred vision. After admission, blood lactate levels were significantly higher than normal. The patients underwent magnetic resonance imaging of the head. Cases 1 and 2 were considered to have ME, whereas case 3 was considered to have a space-occupying lesion in the left temporal lobe. Pathological evaluation showed no obvious tumor cells in the brain lesions of case 3. Muscle biopsy or genetic test results were consistent with ME. The patients were diagnosed with MELAS syndrome and their symptoms improved with intravenous infusions of coenzyme Q10, coenzyme A, vitamin B, and vitamin C. At the 6 mo follow-up, there was no recurrence or progression. CONCLUSION When a patient has MELAS syndrome, familial MELAS syndrome should be considered if related family members have similar symptoms.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Familial mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome: Three case reports

Xiao¹,

Fu²

2022

WJCC

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“…In fact, modifications of tRNA caused by mutations are linked to numerous mitochondrial and neurological diseases [ 37 , 51 ]. By literature searching, we also noticed that m.12308A>G of tRNA Leu(CUN) had been reported to be associated with mitochondrial encephalomyopathies [ 52 ] and syndromes of Wolfram and chronic progressive external ophthalmoplegia [ 53 ]. It was also reported to be associated with increased ROS production and considered a risk factor for many diseases such as severe knee osteoarthritis [ 54 ], stroke [ 55 ], breast cancer [ 56 ] and AD in men [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…Whereas, m.12372G>A was found in patients with LHON [ 60 ], a maternally inherited mitochondrial blinding disorder caused by mtDNA mutations and known to be associated with MS [ 13 ]. Moreover, both variants were reported in Creutzfeldt–Jakob disease, a degenerative brain disorder [ 61 ] and in patients with mitochondrial encephalomyopathies [ 52 ]. In addition, previous studies have identified some of the functional effects of these two variants.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA haplogroup analysis in Saudi Arab patients with multiple sclerosis

et al. 2022

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Previous studies have suggested that mitochondrial DNA (mtDNA) variants are associated with multiple sclerosis (MS), a complex neurodegenerative immune-mediated disease of the central nervous system. Since mtDNA is maternally inherited without recombination, specific mtDNA variants defining genetic background are associated with the susceptibility to human diseases. To assess the contribution of mtDNA haplogroups to the predisposition of MS in an Arab population, we analysed sequencing data of mitochondrial genomes from 47 native Saudi Arab individuals including 23 patients with relapsing-remitting MS (RRMS) and 24 healthy controls. All patients and controls could be classified into ten haplogroups. The European-specific haplogroup U was more prevalent in patients than in the controls (26.1% vs. 4.2%), whereas haplogroup T was only present in patients and haplogroups HV and N were only found in controls. Haplogroup U was significantly association with increased risk of MS (odds ratio = 6.26, p<0.05), although the association did not maintain significance after adjustment for multiple comparisons. Haplotype U was more prevalent in patients with younger age of onset (p = 0.006), but there was no relationship between haplotype U and disease severity, disease duration or EDSS and age-matched carriers and non-carriers of haplogroup U (p>0.05). Definition site of haplogroup U include the variant m.12308A>G in MT-TL2 gene which was found to affect highly conserved position within the variable arm of tRNALeu(CUN) and thus may impact mitochondrial protein synthesis, and two other variants namely m.11467A>G in MT-ND4 gene and m.12372G>A in MT-ND5 gene which were previously linked with mitochondrial function. Despite the small number of subjects, which may limit the statistical power of the study, our results showed for the first time a possible contribution of haplogroup U to the predisposition to MS in an Arab population. These findings warrant further validation in a large cohort to distinguish a genuine effect specific to MS from a chance finding due to small sampling.

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

Cited by 2 publications

References 114 publications

Familial mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome: Three case reports

Familial mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome: Three case reports

Mitochondrial DNA haplogroup analysis in Saudi Arab patients with multiple sclerosis

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