Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant
Abstract
:1. Introduction
2. Results
2.1. mtDNA Assessment
2.2. mtDNA Assessment Pre- vs. Post-LT
2.3. mtDNA Assessment Post-AHSCT
3. Discussion
4. Materials and Methods
4.1. Patients and Sampling
4.2. Clinical History and Pre- and Post-LT Tissue Sampling of Patient #1
4.3. LCM of Ileal Samples
4.4. Total DNA Extraction and mtDNA Copy Number and Deletion Quantification
4.5. Statistic
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AHSCT | Allogeneic Hematopoietic Stem Cell |
ddPCR | droplet digital PCR |
LCM | Laser Capture Microdissection |
LT | Liver Transplantation |
mtDNA | Mitochondrial DNA |
MNGIE | Mitochondrial NeuroGastroIntestinal Encephalomyopathy |
TP | Thymidine Phosphorylase |
References
- Hirano, M.; Nishino, I.; Nishigaki, Y.; Martí, R. Thymidine phosphorylase gene mutations cause mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Intern. Med. 2006, 45, 1103. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- El-Hattab, A.W.; Scaglia, F. Mitochondrial DNA depletion syndromes: Review and updates of genetic basis, manifestations, and therapeutic options. Neurotherapeutics 2013, 10, 186–198. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hirano, M.; Carelli, V.; De Giorgio, R.; Pironi, L.; Accarino, A.; Cenacchi, G.; D’Alessandro, R.; Filosto, M.; Martí, R.; Nonino, F.; et al. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network. J. Inherit. Metab. Dis. 2021, 44, 376–387. [Google Scholar] [CrossRef] [PubMed]
- Halter, J.P.; Michael, W.; Schüpbach, M.; Mandel, H.; Casali, C.; Orchard, K.; Collin, M.; Valcarcel, D.; Rovelli, A.; Filosto, M.; et al. Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy. Brain 2015, 138 Pt 10, 2847–2858. [Google Scholar] [CrossRef] [PubMed]
- Zaidman, I.; Elhasid, R.; Gefen, A.; Dovrat, A.Y.; Mutaz, S.; Shaoul, R.; Adiv, O.E.; Mandel, H.; Tal, G. Hematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalopathy: A single-center experience underscoring the multiple factors involved in the prognosis. Pediatr. Blood Cancer 2021, 68, e28926. [Google Scholar] [CrossRef]
- Paisiou, A.; Rogalidou, M.; Pons, R.; Ioannidou, E.; Dimakou, K.; Papadopoulou, A.; Vaz, F.; Vessalas, G.; Goorden, S.; Roelofsen, J.; et al. Mitochondrial neurogastrointestinal encephalomyopathy: Clinical and biochemical impact of allogeneic stem cell transplantation in a Greek patient with one novel. Mol. Genet. Metab. Rep. 2022, 30, 100829. [Google Scholar] [CrossRef]
- D’Angelo, R.; Boschetti, E.; Amore, G.; Costa, R.; Pugliese, A.; Caporali, L.; Gramegna, L.L.; Papa, V.; Vizioli, L.; Capristo, M.; et al. Liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Clinical long-term follow-up and pathogenic implications. J. Neurol. 2020, 267, 3702–3710. [Google Scholar] [CrossRef]
- De Giorgio, R.; Pironi, L.; Rinaldi, R.; Boschetti, E.; Caporali, L.; Capristo, M.; Casali, C.; Cenacchi, G.; Contin, M.; D’Angelo, R.; et al. Liver transplantation for mitochondrial neurogastrointestinal encephalomyopathy. Ann. Neurol. 2016, 80, 448–455. [Google Scholar] [CrossRef]
- Kripps, K.; Nakayuenyongsuk, W.; Shayota, B.J.; Berquist, W.; Gomez-Ospina, N.; Esquivel, C.O.; Concepcion, W.; Sampson, J.B.; Cristin, D.J.; Jackson, W.E.; et al. Successful liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Mol. Genet. Metab. 2020, 130, 58–64. [Google Scholar] [CrossRef]
- Filosto, M.; Scarpelli, M.; Tonin, P.; Lucchini, G.; Pavan, F.; Santus, F.; Parini, R.; Donati, M.A.; Cotelli, M.S.; Vielmi, V.; et al. Course and management of allogeneic stem cell transplantation in patients with mitochondrial neurogastrointestinal encephalomyopathy. J. Neurol. 2012, 259, 2699–2706. [Google Scholar] [CrossRef]
- Gramegna, L.; Pisano, A.; Testa, C.; Manners, D.; D’Angelo, R.; Boschetti, E.; Giancola, F.; Pironi, L.; Caporali, L.; Capristo, M.; et al. Cerebral Mitochondrial Microangiopathy Leads to Leukoencephalopathy in Mitochondrial Neurogastrointestinal Encephalopathy. AJNR Am. J. Neuroradiol. 2018, 39, 427–434. [Google Scholar] [CrossRef] [PubMed]
- Boschetti, E.; D’Angelo, R.; Tardio, M.L.; Costa, R.; Giordano, C.; Accarino, A.; Malagelada, C.; Clavenzani, P.; Tugnoli, V.; Caio, G.; et al. Evidence of enteric angiopathy and neuromuscular hypoxia in patients with mitochondrial neurogastrointestinal encephalomyopathy. Am. J. Physiol. Gastrointest Liver Physiol. 2021, 320, G768–G779. [Google Scholar] [CrossRef] [PubMed]
- Giordano, C.; Sebastiani, M.; Plazzi, G.; Travaglini, C.; Sale, P.; Pinti, M.; Tancredi, A.; Liguori, R.; Montagna, P.; Bellan, M.; et al. Mitochondrial neurogastrointestinal encephalomyopathy: Evidence of mitochondrial DNA depletion in the small intestine. Gastroenterology 2006, 130, 893–901. [Google Scholar] [CrossRef] [PubMed]
- Giordano, C.; d’Amati, G. Evaluation of gastrointestinal mtDNA depletion in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Methods Mol. Biol. 2011, 755, 223–232. [Google Scholar] [CrossRef]
- Nishigaki, Y.; Marti, R.; Hirano, M. ND5 is a hot-spot for multiple atypical mitochondrial DNA deletions in mitochondrial neurogastrointestinal encephalomyopathy. Hum. Mol. Genet. 2004, 13, 91–101. [Google Scholar] [CrossRef]
- Nishigaki, Y.; Martí, R.; Copeland, W.C.; Hirano, M. Site-specific somatic mitochondrial DNA point mutations in patients with thymidine phosphorylase deficiency. J. Clin. Investig. 2003, 111, 1913–1921. [Google Scholar] [CrossRef] [Green Version]
- Giordano, C.; Sebastiani, M.; De Giorgio, R.; Travaglini, C.; Tancredi, A.; Valentino, M.L.; Bellan, M.; Cossarizza, A.; Hirano, M.; D’Amati, G.; et al. Gastrointestinal dysmotility in mitochondrial neurogastrointestinal encephalomyopathy is caused by mitochondrial DNA depletion. Am. J. Pathol. 2008, 173, 1120–1128. [Google Scholar] [CrossRef] [Green Version]
- Filograna, R.; Mennuni, M.; Alsina, D.; Larsson, N.G. Mitochondrial DNA copy number in human disease: The more the better? FEBS Lett. 2021, 595, 976–1002. [Google Scholar] [CrossRef]
- González-Vioque, E.; Torres-Torronteras, J.; Andreu, A.L.; Martí, R. Limited dCTP availability accounts for mitochondrial DNA depletion in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). PLoS Genet. 2011, 7, e1002035. [Google Scholar] [CrossRef]
- Chapman, J.; Ng, Y.S.; Nicholls, T.J. The Maintenance of Mitochondrial DNA Integrity and Dynamics by Mitochondrial Membranes. Life 2020, 10, 164. [Google Scholar] [CrossRef]
- Butow, R.A.; Avadhani, N.G. Mitochondrial signaling: The retrograde response. Mol. Cell. 2004, 14, 1–15. [Google Scholar] [CrossRef]
- Sicurelli, F.; Carluccio, M.A.; Toraldo, F.; Tozzi, M.; Bucalossi, A.; Lenoci, M.; Jacomelli, G.; Micheli, V.; Cardaioli, E.; Mondelli, M.; et al. Clinical and biochemical improvement following HSCT in a patient with MNGIE: 1-year follow-up. J. Neurol. 2012, 259, 1985–1987. [Google Scholar] [CrossRef] [PubMed]
- Cossarizza, A.; Riva, A.; Pinti, M.; Ammannato, S.; Fedeli, P.; Mussini, C.; Esposito, R.; Galli, M. Increased mitochondrial DNA content in peripheral blood lymphocytes from HIV-infected patients with lipodystrophy. Antivir. Ther. 2003, 8, 315–321. [Google Scholar] [CrossRef]
- Caporali, L.; Bello, L.; Tagliavini, F.; La Morgia, C.; Maresca, A.; Di Vito, L.; Liguori, R.; Valentino, M.L.; Cecchin, D.; Pegoraro, E.; et al. DGUOK recessive mutations in patients with CPEO, mitochondrial myopathy, parkinsonism and mtDNA deletions. Brain 2018, 141, e3. [Google Scholar] [CrossRef] [PubMed]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Boschetti, E.; Caporali, L.; D’Angelo, R.; Malagelada, C.; Accarino, A.; Dotti, M.T.; Costa, R.; Cenacchi, G.; Pironi, L.; Rinaldi, R.; et al. Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant. Int. J. Mol. Sci. 2022, 23, 8792. https://doi.org/10.3390/ijms23158792
Boschetti E, Caporali L, D’Angelo R, Malagelada C, Accarino A, Dotti MT, Costa R, Cenacchi G, Pironi L, Rinaldi R, et al. Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant. International Journal of Molecular Sciences. 2022; 23(15):8792. https://doi.org/10.3390/ijms23158792
Chicago/Turabian StyleBoschetti, Elisa, Leonardo Caporali, Roberto D’Angelo, Carolina Malagelada, Anna Accarino, Maria Teresa Dotti, Roberta Costa, Giovanna Cenacchi, Loris Pironi, Rita Rinaldi, and et al. 2022. "Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant" International Journal of Molecular Sciences 23, no. 15: 8792. https://doi.org/10.3390/ijms23158792