Visual rehabilitation training in a patient with large central scotoma due to Leber’s hereditary optic neuropathy

Background. Leber’s hereditary optic neuropathy (LHON) is a disease associated with pathogenetic mutations of mitochondrial DNA which affects predominantly young adult males and leads to loss of central vision, low visual acuity and unstable fixation. The purpose of this study was to allow the patient to establish the best possible fixation in the best area of retinal sensitivity in LHON patient with central scotoma. Methods. A 17 years old patient with confirmed mitochondrial LHON 11778G > A mutation was included in the study. The patient underwent 16 visual rehabilitation sessions — two for each of 8 weeks using the training module available in the equipment — MAIA microperimeter. Visual acuity and standrad microperimetry examination were performed before and 8 weeks period of training. To measure the fixation stability with MAIA microperimeter, P1, P2 and Bivariate Contour Ellipse Area (BCEA) parameters were used. Results. Visual acuity of the trained better eye was 0.08 at the baseline versus 0.063 after 8 weeks training. Fixation stability parameter was P1-21%, P2-64% at the first session versus P1-60%, P2-90% at the last session. BCEA values 29.2°˛ before and 14.2°˛ after training, respectively. Conclusions. Visual training via microperimetry could potentially be a method that improves the fixation stability in patients with LHON.

RNase H1 Regulates Mitochondrial Transcription and Translation via the Degradation of 7S RNA.

RNase H1 is able to recognize DNA/RNA heteroduplexes and to degrade their RNA component. As a consequence, it has been implicated in different aspects of mtDNA replication such as primer formation, primer removal, and replication termination, and significant differences have been reported between control and mutant RNASEH1 skin fibroblasts from patients. However, neither mtDNA depletion nor the presence of deletions have been described in skin fibroblasts while still presenting signs of mitochondrial dysfunction (lower mitochondrial membrane potential, reduced oxygen consumption, slow growth in galactose). Here, we show that RNase H1 has an effect on mtDNA transcripts, most likely through the regulation of 7S RNA and other R-loops. The observed effect on both mitochondrial mRNAs and 16S rRNA results in decreased mitochondrial translation and subsequently mitochondrial dysfunction in cells carrying mutations in RNASEH1

Mitochondrial encephalomyopathy: Towards diagnosis. A case report

Mitochondrial diseases may cause a wide range of central and peripheral nervous system disorders, as well as muscle disorders. The diagnostic workup routinely includes electrophysiological, morphological, neuroimaging and genetic studies. In some cases, the diagnosis may be ascertained only when mitochondrial DNA (mtDNA) examination in the muscle is performed. We report on a case of a 24-year-old woman, with a 7-year history of slowly progressive cerebellar syndrome and bilateral ptosis. Mitochondrial encephalomyopathy was suspected, based on the clinical picture and results of examinations, but the typical red ragged fibers were not found in the muscle biopsy. The results of molecular analysis of mtDNA showed a mtDNA deletion in the muscle and, on a level detectable only with polymerase chain reaction method, in blood leukocytes. This case emphasizes the important role of mtDNA studies in muscle in nonspecific multisystem mitochondrial disorders, even without clinical muscle involvement

RNase H1 Regulates Mitochondrial Transcription and Translation via the Degradation of 7S RNA

RNase H1 is able to recognize DNA/RNA heteroduplexes and to degrade their RNA component. As a consequence, it has been implicated in different aspects of mtDNA replication such as primer formation, primer removal, and replication termination, and significant differences have been reported between control and mutant RNASEH1 skin fibroblasts from patients. However, neither mtDNA depletion nor the presence of deletions have been described in skin fibroblasts while still presenting signs of mitochondrial dysfunction (lower mitochondrial membrane potential, reduced oxygen consumption, slow growth in galactose). Here, we show that RNase H1 has an effect on mtDNA transcripts, most likely through the regulation of 7S RNA and other R-loops. The observed effect on both mitochondrial mRNAs and 16S rRNA results in decreased mitochondrial translation and subsequently mitochondrial dysfunction in cells carrying mutations in RNASEH1

RNase H1 Regulates Mitochondrial Transcription and Translation via the Degradation of 7S RNA.

RNase H1 is able to recognize DNA/RNA heteroduplexes and to degrade their RNA component. As a consequence, it has been implicated in different aspects of mtDNA replication such as primer formation, primer removal, and replication termination, and significant differences have been reported between control and mutant RNASEH1 skin fibroblasts from patients. However, neither mtDNA depletion nor the presence of deletions have been described in skin fibroblasts while still presenting signs of mitochondrial dysfunction (lower mitochondrial membrane potential, reduced oxygen consumption, slow growth in galactose). Here, we show that RNase H1 has an effect on mtDNA transcripts, most likely through the regulation of 7S RNA and other R-loops. The observed effect on both mitochondrial mRNAs and 16S rRNA results in decreased mitochondrial translation and subsequently mitochondrial dysfunction in cells carrying mutations in RNASEH1

Trudności w diagnostyce zespołu ataksja–neuropatia uwarunkowanego zaburzeniami podjednostki polimerazy DNA gamma (POLG) — prezentacja dwóch przypadków

Rodzinne występowanie ataksji jest wskazaniem do pogłębiania diagnostyki w ramach badań genetycznych. Obecność objawów wśród rodzeństwa, a jednocześnie ich brak u rodziców może sugerować dziedziczenie autosomalne recesywne. Przypadki przedstawione w niniejszej pracy wskazują na zasadność uwzględnienia w diagnostyce różnicowej chorób mitochondrialnych. Mimo że są one związane z wariantami mitochondrialnego DNA (mtDNA), niektóre z nich mogą być dziedziczone w sposób autosomalny, tak jak w przypadku spektrum chorób wynikających z zaburzenia funkcjonowania mitochondrialnej polimerazy DNA gamma. W przedstawionej pracy korelacja obrazu klinicznego oraz hiperintensywność w obrębie wzgórza w badaniu rezonansu magnetycznego były przesłankami do wysunięcia podejrzenia zespołu ataksja–neuropatia spowodowanego wariantami w obrębie genu POLG kodującego podjednostkę katalityczną polimerazy gamma (POLG)

Mitochondrial DNA in pediatric leukemia patients

Numerous studies of mitochondrial DNA (mtDNA) in cancer have shown differences between mtDNA sequences in tumor and normal tissue and at various stages of cancer treatment in the same patient. However, there is little data on acute lymphoblastic leukemia (ALL), the most common type of leukemia in children. In this study we compared mitochondrial sequence variation in the D-loop region and in 5 genes of mtDNA in bone marrow samples of 6 pediatric patients with ALL at various stages of therapy. We found several common polymorphisms and one variant at position 3688 whose level varied during leukemia treatment. Our results suggest that mitochondrial DNA mutations, whose levels change during patient treatment, could be potential biomarkers for monitoring treatment efficacy and disease progression

Comparison between the Polish population and European populations on the basis of mitochondrial morphs and haplogroups.

Polymorphisms in mitochondrial DNA (mtDNA) were analyzed in 152 samples from the Polish population using restriction enzymes AvaI, BamHI, HaeII, HpaI and PstI. Additionally, each sample was classified into the appropriate haplogroup. When required, appropriate fragments were sequenced to establish the exact polymorphic sites. We found one new morph for PstI and six new morphs for AvaII. Some detected morphs have previously been described as population specific morphs in different regions of the world. All polymorphisms were classified into 31 different haplotypes. 21 of them were detected in single individuals. The Polish population was compared with other populations from different regions. Moreover, we have obtained evidence for mutation hot spots in the mtDNA coding region. Our results indicate that AvaII morph and haplogroup composition of the Polish population is similar to other European populations and has a distribution typical for this part of the world. However, statistically significant differences in haplogroup composition were found between the Polish population and Italian and Finnish populations

Heteroplasmy analysis in the Polish patients with 11778A mutation responsible for Leber hereditary optic neuropathy.

We have analysed the heteroplasmy level in 11 individuals from 3 families harbouring the mitochondrial 11778A mutation responsible for Leber hereditary optic neuropathy using last cycle hot PCR. The mutation level exceeded 90% both in affected and in unaffected individuals. We also checked whether any of the families belonged to the J haplogroup of mitochondrial DNA and obtained a negative result

To Be a Champion of the 24-h Ultramarathon Race. If Not the Heart ... Mosaic Theory?

This comprehensive case analysis aimed to identify the features enabling a runner to achieve championship in 24-h ultramarathon (UM) races. A 36-year-old, multiple medalist of the World Championships in 24-h running, was assessed before, one and 10 days after a 24-h run. Results of his extensive laboratory and cardiological diagnostics with transthoracic echocardiography (TTE) and a one-time cardiopulmonary exercise test (CPET) were analyzed. After 12 h of running (approximately 130 km), the athlete experienced an increasing pain in the right knee. His baseline clinical data were within the normal range. High physical efficiency in CPET (VO2max 63 mL/kg/min) was similar to the average achieved by other ultramarathoners who had significantly worse results. Thus, we also performed genetic tests and assessed his psychological profile, body composition, and markers of physical and mental stress (serotonin, cortisol, epinephrine, prolactin, testosterone, and luteinizing hormone). The athlete had a mtDNA haplogroup H (HV0a1 subgroup, belonging to the HV cluster), characteristic of athletes with the highest endurance. Psychological studies have shown high and very high intensity of the properties of individual scales of the tools used mental resilience (62–100% depending on the scale), openness to experience (10th sten), coherence (10th sten), positive perfectionism (100%) and overall hope for success score (10th sten). The athlete himself considers the commitment and mental support of his team to be a significant factor of his success. Body composition assessment (%fat 13.9) and the level of stress markers were unremarkable. The tested athlete showed a number of features of the champions of ultramarathon runs, such as: inborn predispositions, mental traits, level of training, and resistance to pain. However, none of these features are reserved exclusively for “champions”. Team support’s participation cannot be underestimated. The factors that guarantee the success of this elite 24-h UM runner go far beyond physiological and psychological explanations. Further studies are needed to identify individual elements of the putative “mosaic theory of being a champion”