Publications by authors named "E Konarikova"
Article Synopsis
- Mitochondrial diseases are serious inherited disorders primarily affecting children, linked to issues with the mitochondrial energy production system known as oxidative phosphorylation (OXPHOS).
- While mitochondrial DNA mutations account for only 25% of pediatric cases and next-gen sequencing can be inconclusive, biochemical methods remain important for accurate diagnosis.
- The study introduced a method for isolating and cryopreserving peripheral blood mononuclear cells (PBMCs) from children's blood, achieving a 72% diagnosis confirmation rate in mitochondrial disease cases using high-resolution oxygraphy, though false negatives occurred in 13% of instances.
Mitochondrial disorders manifest enormous genetic and clinical heterogeneity - they can appear at any age, present with various phenotypes affecting any organ, and display any mode of inheritance. What mitochondrial diseases do have in common, is impairment of respiratory chain activity, which is responsible for more than 90% of energy production within cells. While diagnostics of mitochondrial disorders has been accelerated by introducing Next-Generation Sequencing techniques in recent years, the treatment options are still very limited.
View Article and Find Full Text PDFThe accurate quantification of cellular and mitochondrial bioenergetic activity is of great interest in medicine and biology. Mitochondrial stress tests performed with Seahorse Bioscience XF Analyzers allow the estimation of different bioenergetic measures by monitoring the oxygen consumption rates (OCR) of living cells in multi-well plates. However, studies of the statistical best practices for determining aggregated OCR measurements and comparisons have been lacking.
View Article and Find Full Text PDFRespiratory chain complex I deficiency is the most frequently identified biochemical defect in childhood mitochondrial diseases. Clinical symptoms range from fatal infantile lactic acidosis to Leigh syndrome and other encephalomyopathies or cardiomyopathies. To date, disease-causing variants in genes coding for 27 complex I subunits, including 7 mitochondrial DNA genes, and in 11 genes encoding complex I assembly factors have been reported.
View Article and Find Full Text PDFArticle Synopsis
- Many patients with Mendelian disorders don't receive genetic diagnoses despite exome sequencing, largely due to variants in non-coding regions.
- This study highlights the effectiveness of transcriptome sequencing, successfully diagnosing 10% of mitochondriopathy patients and suggesting genes for others.
- Researchers identified key genetic anomalies in patient fibroblasts, including aberrant gene expressions and splicing events, and discovered a new disease-associated gene linked to a certain complex in mitochondrial function.