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Trifunov S, Paredes-Fuentes AJ, Badosa C, et al. Circulating Cell-Free Mitochondrial DNA in Cerebrospinal Fluid as a Biomarker for Mitochondrial Diseases. Clin Chem. 2021;67(8):1113-1121doi: 10.1093/clinchem/hvab091.
Trifunov, S., Paredes-Fuentes, A. J., Badosa, C., Codina, A., Montoya, J., Ruiz-Pesini, E., Jou, C., Garrabou, G., Grau-Junyent, J. M., Yubero, D., Montero, R., Muchart, J., Ortigoza-Escobar, J. D., O'Callaghan, M. M., Nascimento, A., Català, A., Garcia-Cazorla, �. �., Jimenez-Mallebrera, C., & Artuch, R. (2021). Circulating Cell-Free Mitochondrial DNA in Cerebrospinal Fluid as a Biomarker for Mitochondrial Diseases. Clinical chemistry, 67(8), 1113-1121. https://doi.org/10.1093/clinchem/hvab091
Trifunov, Selena, et al. "Circulating Cell-Free Mitochondrial DNA in Cerebrospinal Fluid as a Biomarker for Mitochondrial Diseases." Clinical chemistry vol. 67,8 (2021): 1113-1121. doi: https://doi.org/10.1093/clinchem/hvab091
Trifunov S, Paredes-Fuentes AJ, Badosa C, Codina A, Montoya J, Ruiz-Pesini E, Jou C, Garrabou G, Grau-Junyent JM, Yubero D, Montero R, Muchart J, Ortigoza-Escobar JD, O'Callaghan MM, Nascimento A, Català A, Garcia-Cazorla À, Jimenez-Mallebrera C, Artuch R. Circulating Cell-Free Mitochondrial DNA in Cerebrospinal Fluid as a Biomarker for Mitochondrial Diseases. Clin Chem. 2021 Aug 05;67(8):1113-1121. doi: 10.1093/clinchem/hvab091. PMID: 34352085.
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Clin Chem. 2021 Aug 05;67(8):1113-1121. doi: 10.1093/clinchem/hvab091.

Circulating Cell-Free Mitochondrial DNA in Cerebrospinal Fluid as a Biomarker for Mitochondrial Diseases.

Clinical chemistry

Selena Trifunov, Abraham J Paredes-Fuentes, Carmen Badosa, Anna Codina, Julio Montoya, Eduardo Ruiz-Pesini, Cristina Jou, Glòria Garrabou, Josep M Grau-Junyent, Dèlia Yubero, Raquel Montero, Jordi Muchart, Juan D Ortigoza-Escobar, Maria M O'Callaghan, Andrés Nascimento, Albert Català, Àngels Garcia-Cazorla, Cecilia Jimenez-Mallebrera, Rafael Artuch

Affiliations

  1. Neuromuscular Unit, Department of Neuropediatrics, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain.
  2. Department of Clinical Biochemistry, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain.
  3. Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
  4. Department of Biochemistry and Molecular Biology, Institute for Health Research of Aragón (IISAragón), University of Zaragoza, Zaragoza, Spain.
  5. Department of Pathology, Hospital Sant Joan de Déu, Barcelona, Spain.
  6. Department of Internal Medicine, Laboratory of Muscle Research and Mitochondrial Function-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine and Health Science, University of Barcelona (UB), Hospital Clínic of Barcelona (HCB), Barcelona, Spain.
  7. Department of Genetics and Molecular Medicine, Institut de Recerca Sant Joan de Déu, Barcelona, Spain.
  8. Department of Radiology, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain.
  9. Department of Child Neurology, Hospital Sant Joan de Déu, Barcelona, Spain.
  10. Department of Hematology, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain.

PMID: 34352085 DOI: 10.1093/clinchem/hvab091

Abstract

BACKGROUND: Mitochondrial diseases (MD) are genetic metabolic disorders that impair normal mitochondrial structure or function. The aim of this study was to investigate the status of circulating cell-free mitochondrial DNA (ccfmtDNA) in cerebrospinal fluid (CSF), together with other biomarkers (growth differentiation factor-15 [GDF-15], alanine, and lactate), in a cohort of 25 patients with a molecular diagnosis of MD.

METHODS: Measurement of ccfmtDNA was performed by using droplet digital PCR.

RESULTS: The mean copy number of ccfmtDNA was approximately 6 times higher in the MD cohort compared to the control group; patients with mitochondrial deletion and depletion syndromes (MDD) had the higher levels. We also detected the presence of both wild-type mtDNA and mtDNA deletions in CSF samples of patients with single deletions. Patients with MDD with single deletions had significantly higher concentrations of GDF-15 in CSF than controls, whereas patients with point mutations in mitochondrial DNA presented no statistically significant differences. Additionally, we found a significant positive correlation between ccfmtDNA levels and GDF-15 concentrations (r = 0.59, P = 0.016).

CONCLUSION: CSF ccfmtDNA levels are significantly higher in patients with MD in comparison to controls and, thus, they can be used as a novel biomarker for MD research. Our results could also be valuable to support the clinical outcome assessment of MD patients.

© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: [email protected].

Keywords: cerebrospinal fluid; circulating cell-free mitochondrial DNA; droplet digital PCR; mitochondrial deletion and depletion syndromes; mitochondrial diseases

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