Heteroplasmy and Copy Number in the Common m.3243A>G Mutation—A Post-Mortem Genotype–Phenotype Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient
2.2. Literature Cases
2.3. Muscle Histopathology-Patient
2.4. Restriction Fragment Length Polymorphism (RFLP)-Polymerase Chain Reaction (PCR)-Patient
2.5. Determination of mtDNA Copy Numbers-Patient
2.6. Ethical Statement
2.7. Statistical Analysis
3. Results
3.1. Muscle Histopathology (Patient)
3.2. Analysis of Heteroplasmy Levels and Copy Number (Patient)
3.3. Analysis of Clinical Phenotype and Genotype in the Patient and Literature Cases
4. Discussion
5. Limitations
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Literature Case Number | Reference | Sex | MELAS-Phenotype | Deceased Age (Years) | Methods of mtDNA Heteroplasmy Determination |
---|---|---|---|---|---|
L1 | Prasad et al. 2014 [13] | Male | Yes | 18 | PCR, restriction enzyme ApaI; quantitative densitometry |
L2 | Prasad et al. 2014 [13] | Female | No | 65 | PCR, restriction enzyme ApaI; quantitative densitometry |
L3 | Enter et al. 1991 [14] | Female | Yes | 12 | PCR, restriction endonuclease ApaI; mutation detection by PCR |
L4 | Fornuskova et al. 2008 [15] | Female | No | 18 | PCR, restriction enzyme ApaI; quantified with ImageQuant software |
L5 | Cardaioli et al. 1999 [16] | stillbirth | No | Miscarriage (25 weeks) | PCR, restriction enzyme ApaI, autoradiography–quantified with ultra-scan densitometer |
L6 | Ciafaloni et al. 1991 [17] | Male | Yes | 26 | PCR, restriction enzyme HaeIII, quantified with Betascope 603 blot analyser. |
L7 | Kobayashi et al. 1992 [10] | n.k. | Yes | 20 | PCR, restriction enzyme ApaI; autoradiography, quantified with Fujix bioimaging analyser (BAS2000) |
L8 | Macmillan et al. 1993 [18] | Female | Yes | 24 | PCR, restriction enzyme ApaI; quantified on a molecular dyanmics series 4000 phosphorImager |
L9 | Obermaier-Kusser et al. 1991 [19] | Female | Yes | 12 | PCR, restriction enzyme ApaI; densitometry using Elscript 400 UVR scanner |
L10 | Shiraiwa et al. 1993 [20] | Female | Yes | 27 | PCR, restriction enzyme ApaI; autoradiography, quantified with Fujix bioimaging analyser (BAS2000) |
L11 | Shoji et al. 1993 [21] | Female | Yes | 22 | PCR, restriction enzyme ApaI; autoradiography, quantified with a densitometer |
L12 | Hamazaki et al. 1993 [12] | Female | Yes | 14 | PCR, restriction enzyme ApaI; quantified using laser densitometer |
L13 | Koga et al. 2000 [22] | Male | Yes | 10.8 | PCR, restriction enzyme HaeIII, quantified using a Betascope 603 blot analyser. |
L14 | Matthews et al. 1994 [23] | Female | No | 42 | PCR, restriction enzyme ApaI; analysed densitometrically from film negatives |
L15 | Matthews et al. 1994 [23] | n.k. | No | stillborn (24 weeks) | PCR, restriction enzyme ApaI; analysed densitometrically from film negatives |
Tissue Type (Origin) | Heteroplasmy Levels (%) by RFLP | mtDNA Copy Number MT-ND1/18S5 |
---|---|---|
Central nervous system | ||
Putamen | 80.84 | 12.85 |
Caudate nucleus | 79.26 | 24.81 |
Mammillary body | 76.80 | 29.66 |
Hypothalamus | 75.70 | 15.88 |
Thalamus | 74.71 | 33.06 |
Internal capsule | 76.71 | 15.83 |
Globus pallidus | 84.63 | 23.22 |
Visual cortex | 83.67 | 17.79 |
Pons | 90.04 | 6.81 |
Medulla oblongata | 90.75 | 21.41 |
White matter | 90.69 | 9.72 |
Cerebellar vermis | 89.43 | 21.51 |
Spinal cord | 90.53 | 10.42 |
Dorsal root ganglion | 91.16 | 2.31 |
Peripheral organs | ||
Liver | 78.48 | 8.75 |
Bladder | 82.02 | 11.06 |
M. obliqus superior | 72.93 | 24.35 |
M. rectus medialis | 71.37 | 29.95 |
M. rectus superior | 73.02 | 36.17 |
M. rectus inferior | 71.36 | 23.43 |
M. iliopsoas | 68.16 | 36.29 |
M. vastus lat. | 65.91 | 14.65 |
M. pectoralis | 73.68 | 12.76 |
M. biceps brachii | 81.20 | 20.08 |
Tongue muscle base | 84.64 | 15.73 |
Heart muscle (left) | 81.40 | 27.16 |
Heart muscle (right) | 77.04 | 11.64 |
AV-node | 71.38 | 12.60 |
Kidney | 63.28 | 12.42 |
Sural nerve | 90.76 | 6.25 |
Significant | p-Value | MELAS (Mean) | Non-MELAS (Mean) | |
---|---|---|---|---|
Deceased Age | No | 0.266411820 | 18.58 | 28.53 |
Skeletal | No | 0.108486887 | 77.8 | 62.5 |
Cardiac | No | 0.059542563 | 78.44 | 64.25 |
Liver | Yes | 0.011731624 | 80.56 | 58.33 |
Kidney | Yes | 0.006090533 | 82 | 39.25 |
Brain | No | 0.059855928 | 82.89 | 68.2 |
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Motlagh Scholle, L.; Zierz, S.; Mawrin, C.; Wickenhauser, C.; Lehmann Urban, D. Heteroplasmy and Copy Number in the Common m.3243A>G Mutation—A Post-Mortem Genotype–Phenotype Analysis. Genes 2020, 11, 212. https://doi.org/10.3390/genes11020212
Motlagh Scholle L, Zierz S, Mawrin C, Wickenhauser C, Lehmann Urban D. Heteroplasmy and Copy Number in the Common m.3243A>G Mutation—A Post-Mortem Genotype–Phenotype Analysis. Genes. 2020; 11(2):212. https://doi.org/10.3390/genes11020212
Chicago/Turabian StyleMotlagh Scholle, Leila, Stephan Zierz, Christian Mawrin, Claudia Wickenhauser, and Diana Lehmann Urban. 2020. "Heteroplasmy and Copy Number in the Common m.3243A>G Mutation—A Post-Mortem Genotype–Phenotype Analysis" Genes 11, no. 2: 212. https://doi.org/10.3390/genes11020212
APA StyleMotlagh Scholle, L., Zierz, S., Mawrin, C., Wickenhauser, C., & Lehmann Urban, D. (2020). Heteroplasmy and Copy Number in the Common m.3243A>G Mutation—A Post-Mortem Genotype–Phenotype Analysis. Genes, 11(2), 212. https://doi.org/10.3390/genes11020212