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Circulating Cell-Free Mitochondrial DNA in Cerebrospinal Fluid as a Biomarker for Mitochondrial Diseases
Selena Trifunov1, Abraham J Paredes-Fuentes2, Carmen Badosa1
1Neuromuscular Unit, Department of Neuropediatrics, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain.
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.
Insights
Circulating cell-free mitochondrial DNA (ccfmtDNA) in cerebrospinal fluid is significantly elevated in patients with mitochondrial diseases (MD). This finding suggests ccfmtDNA may serve as a novel biomarker for MD diagnosis and research.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Mitochondrial diseases (MD) are genetic metabolic disorders affecting mitochondrial function.
- Investigating biomarkers in cerebrospinal fluid (CSF) is crucial for understanding MD pathogenesis.
Purpose of the Study:
- To assess circulating cell-free mitochondrial DNA (ccfmtDNA) levels in CSF of MD patients.
- To evaluate other potential biomarkers including GDF-15, alanine, and lactate.
Main Methods:
- Droplet digital PCR was utilized for ccfmtDNA quantification.
- Analysis included a cohort of 25 patients with molecularly diagnosed MD and controls.
Main Results:
- ccfmtDNA levels were approximately 6-fold higher in MD patients compared to controls.
- Elevated ccfmtDNA and GDF-15 were observed in patients with mitochondrial deletion and depletion syndromes (MDD).
- A positive correlation was found between ccfmtDNA and GDF-15 concentrations.
Conclusions:
- CSF ccfmtDNA serves as a promising novel biomarker for MD.
- These findings can aid in the clinical outcome assessment of MD patients.
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