scholarly journals Mitochondrial A3243G mutation causes mitochondrial encephalomyopathy in a Chinese patient

Medicine ◽  
2019 ◽  
Vol 98 (19) ◽  
pp. e15534 ◽  
Author(s):  
Xiao-Qun Liu ◽  
Shao-Qing Shen ◽  
Guo-Can Yang ◽  
Qi Liu
Keyword(s):  
Chinese Patient ◽  
Mitochondrial Encephalomyopathy ◽  
A3243g Mutation

scholarly journals Clinical Characteristics of Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1111
Author(s):  
Hueng-Chuen Fan ◽  
Hsiu-Fen Lee ◽  
Chen-Tang Yue ◽  
Ching-Shiang Chi
Keyword(s):  
Lactic Acidosis ◽  
Mitochondrial Disorder ◽  
Chain Complex ◽  
Mitochondrial Encephalomyopathy ◽  
Common Mutation ◽  
Melas Syndrome ◽  
Mitochondrial Translation ◽  
Gene Encoding ◽  
Clinical Complexity ◽  
A3243g Mutation

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes(MELAS)syndrome, a maternally inherited mitochondrial disorder, is characterized by its genetic, biochemical and clinical complexity. The most common mutation associated with MELAS syndrome is the mtDNA A3243G mutation in the MT-TL1 gene encoding the mitochondrial tRNA-leu(UUR), which results in impaired mitochondrial translation and protein synthesis involving the mitochondrial electron transport chain complex subunits, leading to impaired mitochondrial energy production. Angiopathy, either alone or in combination with nitric oxide (NO) deficiency, further contributes to multi-organ involvement in MELAS syndrome. Management for MELAS syndrome is amostly symptomatic multidisciplinary approach. In this article, we review the clinical presentations, pathogenic mechanisms and options for management of MELAS syndrome.

Phenotypic Analysis of Epilepsy in the Mitochondrial Encephalomyopathy, Lactic Acidosis, and Strokelike Episodes–Associated Mitochondrial DNA A3243G Mutation

2014 ◽  
Vol 29 (9) ◽  
pp. 1249-1256 ◽  
Author(s):  
Scott T. Demarest ◽  
Matthew T. Whitehead ◽  
Sinan Turnacioglu ◽  
Phillip L. Pearl ◽  
Andrea L. Gropman
Keyword(s):  
Mitochondrial Dna ◽  
Lactic Acidosis ◽  
Mitochondrial Encephalomyopathy ◽  
Phenotypic Analysis ◽  
A3243g Mutation

scholarly journals Design and Use of a Peptide Nucleic Acid for Detection of the Heteroplasmic Low-Frequency Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS) Mutation in Human Mitochondrial DNA

2002 ◽  
Vol 48 (12) ◽  
pp. 2155-2163 ◽  
Author(s):  
Diane K Hancock ◽  
Frederick P Schwarz ◽  
Fenhong Song ◽  
Lee-Jun C Wong ◽  
Barbara C Levin
Keyword(s):  
Mitochondrial Dna ◽  
Lactic Acidosis ◽  
Low Frequency ◽  
Pcr Amplification ◽  
Mitochondrial Encephalomyopathy ◽  
Nucleotide Position ◽  
Wild Type ◽  
Human Mitochondrial Dna ◽  
Mtdna Mutations ◽  
A3243g Mutation

Abstract Background: Most pathogenic human mitochondrial DNA (mtDNA) mutations are heteroplasmic (i.e., mutant and wild-type mtDNA coexist in the same individual) and are difficult to detect when their concentration is a small proportion of that of wild-type mtDNA molecules. We describe a simple methodology to detect low proportions of the single base pair heteroplasmic mutation, A3243G, that has been associated with the disease mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) in total DNA extracted from blood. Methods: Three peptide nucleic acids (PNAs) were designed to bind to the wild-type mtDNA in the region of nucleotide position 3243, thus blocking PCR amplification of the wild-type mtDNA while permitting the mutant DNA to become the dominant product and readily discernable. DNA was obtained from both apparently healthy and MELAS individuals. Optimum PCR temperatures were based on the measured ultraviolet thermal stability of the DNA/PNA duplexes. The presence or absence of the mutation was determined by sequencing. Results: In the absence of PNAs, the heteroplasmic mutation was either difficult to detect or undetectable by PCR and sequencing. Only PNA 3 successfully inhibited amplification of the wild-type mtDNA while allowing the mutant mtDNA to amplify. In the presence of PNA 3, we were able to detect the heteroplasmic mutation when its concentration was as low as 0.1% of the concentration of the wild-type sequence. Conclusion: This methodology permits easy detection of low concentrations of the MELAS A3243G mutation in blood by standard PCR and sequencing methods.

scholarly journals Human Mitochondrial Leucyl-tRNA Synthetase Corrects Mitochondrial Dysfunctions Due to the tRNALeu(UUR) A3243G Mutation, Associated with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Symptoms and Diabetes

2010 ◽  
Vol 30 (9) ◽  
pp. 2147-2154 ◽  
Author(s):  
Ronghua Li ◽  
Min-Xin Guan
Keyword(s):  
Lactic Acidosis ◽  
Molecular Mechanism ◽  
Wide Spectrum ◽  
Trna Synthetase ◽  
Mitochondrial Encephalomyopathy ◽  
Therapeutic Interventions ◽  
Trna Genes ◽  
Mitochondrial Translation ◽  
Mitochondrial Dysfunctions ◽  
A3243g Mutation

ABSTRACT Mutations in mitochondrial tRNA genes are associated with a wide spectrum of human diseases. In particular, the tRNALeu(UUR) A3243G mutation causes mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms (MELAS) and 2% of cases of type 2 diabetes. The primary defect in this mutation was an inefficient aminoacylation of the tRNALeu(UUR). In the present study, we have investigated the molecular mechanism of the A3243G mutation and whether the overexpression of human mitochondrial leucyl-tRNA synthetase (LARS2) in the cytoplasmic hybrid (cybrid) cells carrying the A3243G mutation corrects the mitochondrial dysfunctions. Human LARS2 localizes exclusively to mitochondria, and LARS2 is expressed ubiquitously but most abundantly in tissues with high metabolic rates. We showed that the alteration of aminoacylation tRNALeu(UUR) caused by the A3243G mutation led to mitochondrial translational defects and thereby reduced the aminoacylated efficiencies of tRNALeu(UUR) as well as tRNAAla and tRNAMet. We demonstrated that the transfer of human mitochondrial leucyl-tRNA synthetase into the cybrid cells carrying the A3243G mutation improved the efficiency of aminoacylation and stability of mitochondrial tRNAs and then increased the rates of mitochondrial translation and respiration, consequently correcting the mitochondrial dysfunction. These findings provide new insights into the molecular mechanism of maternally inherited diseases and a step toward therapeutic interventions for these disorders.

CLIPPERS syndrome: A case report in a Chinese patient with juxtacortical lesions

2021 ◽  
Vol 50 ◽  
pp. 102853
Author(s):  
Haiqiang Jin ◽  
Yuhan Gao ◽  
Qianshuo Lu ◽  
Ran Liu ◽  
Qunyan Li ◽  
...  
Keyword(s):  
Case Report ◽  
Chinese Patient

scholarly journals General anesthesia with remimazolam in a patient with mitochondrial encephalomyopathy: a case report

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yuji Suzuki ◽  
Matsuyuki Doi ◽  
Yoshiki Nakajima
Keyword(s):  
Lactic Acidosis ◽  
General Anesthesia ◽  
Mitochondrial Disease ◽  
Muscle Relaxation ◽  
Anesthetic Management ◽  
Perioperative Period ◽  
Mitochondrial Encephalomyopathy ◽  
Anesthesia Induction ◽  
General Anesthetic ◽  
Anesthetic Agents

Abstract Background Systemic anesthetic management of patients with mitochondrial disease requires careful preoperative preparation to administer adequate anesthesia and address potential disease-related complications. The appropriate general anesthetic agents to use in these patients remain controversial. Case presentation A 54-year-old woman (height, 145 cm; weight, 43 kg) diagnosed with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes underwent elective cochlear implantation. Infusions of intravenous remimazolam and remifentanil guided by patient state index monitoring were used for anesthesia induction and maintenance. Neither lactic acidosis nor prolonged muscle relaxation occurred in the perioperative period. At the end of surgery, flumazenil was administered to antagonize sedation, which rapidly resulted in consciousness. Conclusions Remimazolam administration and reversal with flumazenil were successfully used for general anesthesia in a patient with mitochondrial disease.

Sign in / Sign up

Export Citation Format

Share Document