Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review
Abstract
:1. Introduction
2. Patients and Methods
2.1. Patients
2.2. Ethical Considerations
2.3. Molecular Genetic Methods
2.4. Haplogroups Analysis and Phylogenetic Tree Reconstruction
2.5. Bioinformatics Analysis
3. Results
3.1. Mutational Genetic Analysis
3.2. MITOMASTER Analysis
3.3. Phylogenetic Tree Construction
3.4. Genotype-Phenotype Relationship
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Mitochondriopathies | MELAS | Leigh Disease |
---|---|---|
Mutation | m.3243A>G | m.8993T>G |
Gene | RNA Gene MT-TL1 | Protein Coding gene MT-ATP6 |
Codon number | − | 156 |
Amino acid change | tRNA Leu | Leu-Arg |
Mitomap | Confirmed-Pathogenic | Confirmed-Pathogenic |
MitoTIP | Pathogenic | − |
Mamit-tRNA | Pathogenic | − |
UniProt ID | − | P00846 |
Polyphen Prediction | − | probably damaging |
PANTHER | − | probably damaging |
PROVEAN | − | Deleterious (−5.180) |
Probands | Haplogroup | Variants | Locus | Nucleotide Changes | A.A Changes | PhyloTree Build 17 in HG Branch | Mitomaster Frequencies in HG Branch |
---|---|---|---|---|---|---|---|
P1 | U2e | 73 | MT-CR | A>G | CR | Reported | 96.46% |
(MELAS) | 152 | MT-CR | T>C | CR | Reported | 90.26% | |
263 | MT-CR | A>G | CR | Reported | 96.46% | ||
508 | MT-CR | A>G | CR | Reported | 94.39% | ||
739 | MT-RNR1 | C>T | rRNA | Not reported | 0.29% | ||
750 | MT-RNR1 | A>G | rRNA | Reported | 100.00% | ||
1438 | MT-RNR1 | A>G | rRNA | Reported | 98.82% | ||
1811 | MT-RNR2 | A>G | rRNA | Reported | 94.39% | ||
2706 | MT-RNR2 | A>G | rRNA | Reported | 99.11% | ||
3116 | MT-RNR2 | C>T | rRNA | Not reported | 22.71% | ||
3720 | MT-ND1 | A>G | Q138Q | Reported | 98.23% | ||
4769 | MT-ND2 | A>G | M100M | Reported | 98.52% | ||
5390 | MT-ND2 | A>G | M307M | Reported | 98.52% | ||
5426 | MT-ND3 | T>C | H319H | Reported | 98.52% | ||
6045 | MT-COI | C>T | L48L | Reported | 98.52% | ||
6152 | MT-COI | T>C | V83V | Reported | 98.23% | ||
7028 | MT-COI | C>T | A375A | Reported | 98.80% | ||
8860 | MT-ATP6 | A>G | T112A | Reported | 99.41% | ||
10,876 | MT-ND4 | A>G | L39L | Reported | 99.11% | ||
11,197 | MT-ND4 | C>T | G146G | Not reported | 22.42% | ||
11,467 | MT-ND4 | A>G | L236L | Reported | 98.82% | ||
11,719 | MT-ND4 | G>A | G320G | Reported | 99.40% | ||
12,308 | MT-TL2 | A>G | tRNA | Reported | 98.80% | ||
12,372 | MT-ND5 | G>A | L12L | Reported | 99.70% | ||
13,020 | MT-ND5 | T>C | G228G | Reported | 99.11% | ||
13,359 | MT-ND5 | G>A | M341M | Not reported | 0.00% | ||
14,766 | MT-CYB | C>T | T7I | Reported | 99.70% | ||
15,326 | MT-CYB | A>G | T194A | Reported | 99.70% | ||
15,907 | MT-TT | A>G | tRNA | Reported | 98.82% | ||
16,051 | MT-CR | A>G | CR | Reported | 96.75% | ||
16,129 | MT-CR | G>C | CR | Reported | 95.28% | ||
16,183 | MT-CR | A>C | CR | Not considered | 75.52% | ||
16,189 | MT-CR | T>C | CR | Reported | 84.36% | ||
P2 | H15 | 55 | MT-CR | T>C | CR | Reported | 63.33% |
(MELAS) | 56 | MT-CR | insC | CR | Not reported | 6.67% | |
143 | MT-CR | G>A | CR | Not reported | 0.00% | ||
263 | MT-RNR1 | A>G | CR | Reported | 80.00% | ||
750 | MT-RNR1 | A>G | rRNA | Reported | 100.00% | ||
1438 | MT-RNR2 | A>G | rRNA | Reported | 96.70% | ||
2706 | MT-ND1 | A>G | rRNA | Reported | 95.60% | ||
3847 | MT-ND2 | T>C | L181L | Reported | 96.67% | ||
4769 | MT-COI | A>G | M100M | Reported | 96.70% | ||
6253 | MT-COI | T>C | M117T | Reported | 96.67% | ||
7028 | MT-ATP6 | C>T | A375A | Reported | 97.80% | ||
8860 | MT-CYB | A>G | T112A | Reported | 96.67% | ||
15,326 | MT-CR | A>G | T194A | Reported | 96.70% | ||
P3 | H34 | 152 | MT-CR | T>C | CR | Not reported | 90.91% |
(LS) | 263 | MT-CR | A>G | CR | Reported | 100.00% | |
315 | MT-CR | insC | CR | Not reported | 45.46% | ||
508 | MT-RNR1 | A>G | CR | Not reported | 0.00% | ||
750 | MT-RNR1 | A>G | rRNA | Reported | 100.00% | ||
1438 | MT-RNR1 | A>G | rRNA | Reported | 100.00% | ||
4769 | MT-ND2 | A>G | M100M | Reported | 100.00% | ||
8860 | MT-ATP6 | A>G | T112A | Reported | 100.00% | ||
15,326 | MT-CYB | A>G | T194A | Reported | 100.00% | ||
15,519 | MT-CYB | T>C | L258P | Reported | 100.00% | ||
15,948 | MT-TT | A>G | tRNA | Not reported | 0.00% | ||
16,093 | MT-CR | T>C | CR | Not reported | 45.46% | ||
16,291 | MT-CR | C>T | CR | Reported | 90.91% | ||
16,519 | MT-CR | T>C | CR | Reported | 100.00% |
Clinical Evaluation | MELAS | Leigh Disease | |
---|---|---|---|
Proband | P1 | P2 | P3 |
Gender | Male | Male | Female |
Age at onset of the disease | 14 years old | 12 years old | Few months after birth |
Duration of the disease | 1 month | 9 years | 4 years |
Family history of MEMP | − | – | – |
Epileptic seizures | + | + | + |
Psychosis | + | + | − |
Psychomotor retardation | – | − | + |
Confusion | + | − | − |
Behaviour changes | + | + | + |
Dementia | − | + | − |
Episodes like stroke | − | − | − |
Headache | + | − | − |
Eye deviation during seizures | − | − | + |
Speech delay | − | − | + |
Hemiparesis | + | + | − |
Muscle weakness | + | + | + |
Muscle twitches | + | − | + |
Associated vomiting | + | + | − |
Preceding infection | − | + | + |
Lactate acidosis | + | + | + |
MRI changes | + | + | + |
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Dawod, P.G.A.; Jancic, J.; Marjanovic, A.; Brankovic, M.; Jankovic, M.; Samardzic, J.; Gamil Anwar Dawod, A.; Novakovic, I.; Abdel Motaleb, F.I.; Radlovic, V.; et al. Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review. Diagnostics 2021, 11, 1969. https://doi.org/10.3390/diagnostics11111969
Dawod PGA, Jancic J, Marjanovic A, Brankovic M, Jankovic M, Samardzic J, Gamil Anwar Dawod A, Novakovic I, Abdel Motaleb FI, Radlovic V, et al. Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review. Diagnostics. 2021; 11(11):1969. https://doi.org/10.3390/diagnostics11111969
Chicago/Turabian StyleDawod, Phepy G. A., Jasna Jancic, Ana Marjanovic, Marija Brankovic, Milena Jankovic, Janko Samardzic, Ayman Gamil Anwar Dawod, Ivana Novakovic, Fayda I. Abdel Motaleb, Vladimir Radlovic, and et al. 2021. "Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review" Diagnostics 11, no. 11: 1969. https://doi.org/10.3390/diagnostics11111969
APA StyleDawod, P. G. A., Jancic, J., Marjanovic, A., Brankovic, M., Jankovic, M., Samardzic, J., Gamil Anwar Dawod, A., Novakovic, I., Abdel Motaleb, F. I., Radlovic, V., Kostic, V. S., & Nikolic, D. (2021). Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review. Diagnostics, 11(11), 1969. https://doi.org/10.3390/diagnostics11111969