Circulating Cell-Free Mitochondrial DNA in Cerebrospinal Fluid as a Biomarker for Mitochondrial Diseases
Por:
Trifunov S, Paredes-Fuentes AJ, Badosa-Gallego MC, Codina-Bergadà A, Montoya C, Ruiz-Pesini E, Jou-Munoz C, Garrabou G, Grau-Junyent JM, Yubero-Siles D, Montero-Sanchez R, Muchart-Lopez J, Ortigoza-Escobar JD, O'Callaghan-Gordo M, Nascimento-Osorio A, Català-Temprano A, Garcia-Cazorla A, Jimenez-Mallebrera C and Artuch-Iriberri R
Publicada:
1 ago 2021
Ahead of Print:
1 ago 2021
Resumen:
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.
Filiaciones:
Trifunov S:
Neuromuscular Unit, Department of Neuropediatrics, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
:
Department of Clinical Biochemistry, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Badosa-Gallego MC:
Neuromuscular Unit, Department of Neuropediatrics, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Codina-Bergadà A:
Neuromuscular Unit, Department of Neuropediatrics, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Montoya C:
Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Department of Biochemistry and Molecular Biology, Institute for Health Research of Aragón (IISAragón), University of Zaragoza, Zaragoza, Spain
Ruiz-Pesini E:
Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Department of Biochemistry and Molecular Biology, Institute for Health Research of Aragón (IISAragón), University of Zaragoza, Zaragoza, Spain
Jou-Munoz C:
Neuromuscular Unit, Department of Neuropediatrics, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Department of Pathology, Hospital Sant Joan de Déu, Barcelona, Spain
Garrabou G:
Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
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
Grau-Junyent JM:
Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
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
Yubero-Siles D:
Department of Genetics and Molecular Medicine, Institut de Recerca Sant Joan de Déu, Barcelona, Spain
Montero-Sanchez R:
Department of Clinical Biochemistry, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Muchart-Lopez J:
Department of Radiology, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Ortigoza-Escobar JD:
Department of Child Neurology, Hospital Sant Joan de Déu, Barcelona, Spain
O'Callaghan-Gordo M:
Department of Child Neurology, Hospital Sant Joan de Déu, Barcelona, Spain
Nascimento-Osorio A:
Neuromuscular Unit, Department of Neuropediatrics, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Català-Temprano A:
Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Department of Hematology, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Garcia-Cazorla A:
Department of Child Neurology, Hospital Sant Joan de Déu, Barcelona, Spain
Jimenez-Mallebrera C:
Neuromuscular Unit, Department of Neuropediatrics, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Artuch-Iriberri R:
Neuromuscular Unit, Department of Neuropediatrics, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Hosp St Joan de Deu, Inst Recerca St Joan de Deu, Dept Hematol, Barcelona, Spain.
Hosp St Joan de Deu, Inst Recerca St Joan de Deu, Dept Hematol, Barcelona, Spain
Hosp St Joan de Deu, Inst Recerca St Joan de Deu, Dept Hematol, Barcelona, Spain
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