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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
21

Evaluation of metallothionein involvement in the modulation of mitochondrial respiration in mice / Marianne Pretorius.

Pretorius, Marianne January 2011 (has links)
Metallothioneins (MTs) are small, non-enzymatic proteins that are involved in cellular detoxification and metal homeostasis because of their high cysteine content. MTs have also been identified as one of the vast number of adaptive responses to mitochondrial respiratory chain (RC) deficiencies. Aside from this, numerous other studies have linked MTs to several mitochondrion-linked components, including reactive oxygen species (ROS) and oxidative stress, apoptosis, glutathione, energy metabolism and nuclear- and mitochondrial DNA transcription regulation. However, most of the reports concerning the putative link between MTs and mitochondria are from in vitro studies and relatively little supportive in vivo evidence has been reported. Information on the involvement of MTs with respiratory chain function is especially limited. Is was therefore the aim of this study to investigate the involvement of MTs in mitochondrial respiration and respiratory chain enzyme function by using an MT knockout (MTKO) mouse model, which was treated with the irreversible complex I inhibiting reagent, rotenone. The aim was achieved by implementing three objectives: firstly, the RC function was investigated as a complete working unit; secondly, the functional and structural properties of single units (enzymes) of the RC were investigated utilising enzyme activity assays and BN- PAGE/western blot analysis; and thirdly, the possible effect of MTs on mtDNA copy number was investigated. While some tendencies of variation in RC enzyme activity and expression were identified, no significant effect on the overall mitochondrial respiratory function, or any significant differences in the relative mtDNA copy number of MTKO mice were observed. Thus it is concluded, while MTs have in this study revealed relatively small changes in respiratory chain function, which may still prove to have biological ignificance in vivo, the exact nature of the putative role of MTs in mitochondrial respiration or oxidative phosphorylation remains undefined. / Thesis (MSc (Biochemistry))--North-West University, Potchefstroom Campus, 2012.
22

Evaluation of metallothionein involvement in the modulation of mitochondrial respiration in mice / Marianne Pretorius.

Pretorius, Marianne January 2011 (has links)
Metallothioneins (MTs) are small, non-enzymatic proteins that are involved in cellular detoxification and metal homeostasis because of their high cysteine content. MTs have also been identified as one of the vast number of adaptive responses to mitochondrial respiratory chain (RC) deficiencies. Aside from this, numerous other studies have linked MTs to several mitochondrion-linked components, including reactive oxygen species (ROS) and oxidative stress, apoptosis, glutathione, energy metabolism and nuclear- and mitochondrial DNA transcription regulation. However, most of the reports concerning the putative link between MTs and mitochondria are from in vitro studies and relatively little supportive in vivo evidence has been reported. Information on the involvement of MTs with respiratory chain function is especially limited. Is was therefore the aim of this study to investigate the involvement of MTs in mitochondrial respiration and respiratory chain enzyme function by using an MT knockout (MTKO) mouse model, which was treated with the irreversible complex I inhibiting reagent, rotenone. The aim was achieved by implementing three objectives: firstly, the RC function was investigated as a complete working unit; secondly, the functional and structural properties of single units (enzymes) of the RC were investigated utilising enzyme activity assays and BN- PAGE/western blot analysis; and thirdly, the possible effect of MTs on mtDNA copy number was investigated. While some tendencies of variation in RC enzyme activity and expression were identified, no significant effect on the overall mitochondrial respiratory function, or any significant differences in the relative mtDNA copy number of MTKO mice were observed. Thus it is concluded, while MTs have in this study revealed relatively small changes in respiratory chain function, which may still prove to have biological ignificance in vivo, the exact nature of the putative role of MTs in mitochondrial respiration or oxidative phosphorylation remains undefined. / Thesis (MSc (Biochemistry))--North-West University, Potchefstroom Campus, 2012.
23

Estudo do efeito da quantidade de cópias de DNA mitocondrial sobre o desenvolvimento embrionário = implicações na fertilidade e herança mitocondrial / Study of the effect of mitochondrial DNA amount on embryonic development : implications for fertility and mitochondrial inheritance

Chiaratti, Marcos Roberto 16 August 2018 (has links)
Orientadores: Aníbal Eugênio Vercesi, Flávio Vieira Meirelles / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-16T13:18:47Z (GMT). No. of bitstreams: 1 Chiaratti_MarcosRoberto_D.pdf: 26150066 bytes, checksum: 12cccf5f865b2ef08f186cad0c922cb6 (MD5) Previous issue date: 2010 / Resumo: O DNA mitocondrial (mtDNA) dos mamíferos é composto por cerca de 16.500 pares de bases, tem herança exclusivamente materna, e codifica 13 polipeptídios essenciais para a função mitocondrial. Centenas a milhares de cópias de mtDNA estão presentes nas células somáticas dependendo da necessidade energética do tecido. No entanto, oócitos contêm mais de 150.000 cópias, no mínimo uma ordem de magnitude maior que a quantidade presente na maioria das células somáticas. Além disso, uma vez que o mtDNA não é replicado durante o desenvolvimento inicial, a quantidade de mtDNA por célula diminui a cada ciclo celular. Portanto, o número de cópias presentes no oócito deve ser suficiente para atender às necessidade energéticas das células embrionárias até que a replicação do mtDNA seja restabelecida. Considerando que há uma grande variabilidade da quantidade de mtDNA entre oócitos e que alguns trabalhos têm relacionado infertilidade e cópias de mtDNA no oócito, a quantidade de mtDNA poderia ser utilizada para selecionar embriões mais competentes a se desenvolverem. Para testar esta hipótese utilizou-se como modelo experimental o bovino uma vez que o desenvolvimento embrionário desta espécie é muito mais similar ao do humano que o de camundongo. Para tanto, em um primeiro experimento foram utilizados oócitos bovinos provenientes de folículos de diferentes tamanhos. Oócitos oriundos de folículos pequenos, os quais são sabidamente menos competentes a se desenvolverem a blastocisto, continham menos mtDNA comparado com oócitos oriundos de folículos maiores. No entanto, devido a grande variabilidade do número de cópias, num segundo experimento embriões partenogenéticos no estádio de uma célula sofreram biópsia para se determinar o conteúdo de mtDNA antes de serem cultivados para acessar a capacidade de desenvolvimento. Em contraste com achados prévios, o número de cópias de mtDNA nas biópsias não diferiu entre embriões competentes e incompetentes, indicando que o conteúdo de mtDNA não está relacionado com a competência de desenvolvimento a blastocisto. Para confirmar este achado, embriões no estádio de uma célula foram depletados em mais de 60% do seu conteúdo de mtDNA por centrifugação seguido da remoção de parte da fração citoplasmática rica em mitocôndrias. Surpreendentemente, os embriões depletados desenvolveram-se normalmente a blastocisto, os quais continham número de cópias de mtDNA similar a controles não manipulados. O desenvolvimento dos embriões depletados foi acompanhado por um aumento na expressão de genes (TFAM e NRF1) que controlam a replicação e transcrição do mtDNA, indicando uma habilidade intrínseca do embrião bovino em restaurar o conteúdo de mtDNA no estádio de blastocisto. Em conclusão, embriões bovinos competentes são capazes de regular o conteúdo de mtDNA no estádio de blastocisto independentemente do número de cópias presente no oócito. Estes achados contrariam o que foi descrito em camundongos, ressaltando a necessidade de estudos com espécies mais semelhantes ao homem antes do uso clínico do mtDNA como ferramenta para o diagnóstico de fertilidade em mulheres. Além disso, este trabalho tem implicação na manipulação da herança mitocondrial e, portanto, na prevenção da transmissão de sérias patologias causadas por mutações no mtDNA / Abstract: The mammalian mitochondrial DNA (mtDNA) is composed by only about 16,500 base pairs, is exclusively inherited from the mother, and encodes 13 polypeptides essential for mitochondrial function. Hundreds to thousands mtDNA copies are found in somatic cells depending on the energetic requirement of the tissue. However, oocytes contain more than 150,000 copies, at least an order of magnitude greater than most somatic cells. Moreover, since replication of mtDNA is downregulated during early development, the mtDNA content per cell decreases after each cell cycle. Therefore, mtDNA copy number in oocytes should be enough to support the energetic requirement of embryonic cells until mtDNA replication to be restablished. Considering there is a wide variability of mtDNA copy number among oocytes and there are reports showing a link between infertility and oocyte mtDNA copy number, the content of mtDNA could be used to select embryos more competent to develop. To test this hypothesis we used the bovine as an experimental model since its embryonic development is more similar to human than the murine is. Therefore, in a first experiment bovine oocytes derived from follicles of different sizes were used. Oocytes obtained from small follicles, known to be less competent to develop into blastocysts, contained less mtDNA than those originated from larger follicles. However, due to the high variability in copy number, in a second experiment a more accurate approach was examined in which parthenogenetic one-cell embryos were biopsied to measure their mtDNA content and then cultured to assess development capacity. Contrasting with previous findings, mtDNA copy number in biopsies was not different between competent and incompetent embryos, indicating that mtDNA content is not related to early developmental competence. To further examine the importance of mtDNA on development, one-cell embryos were partially depleted of over than 60% of their mtDNA by centrifugation followed by the removal of the mitochondrial-enriched cytoplasmic fraction. Surprisingly, depleted embryos developed normally into blastocysts, which contained mtDNA copy numbers similar to non-manipulated controls. Development in depleted embryos was accompanied by an increase in the expression of genes (TFAM and NRF1) controlling mtDNA replication and transcription, indicating an intrinsic ability to restore the content of mtDNA at the blastocyst stage. In conclusion, competent bovine embryos are able to regulate their mtDNA content at the blastocyst stage regardless of the copy numbers present in oocytes. These findings are in disagreement with that reported for mice, highlighting the need for studies using species more similar to human before the clinical use of mtDNA as a diagnostic tool in woman fertility. Moreover, these findings are important to manipulate mitochondrial inheritance and, therefore, to prevent transmission of important disorders caused by mtDNA mutations / Doutorado / Biologia Estrutural, Celular, Molecular e do Desenvolvimento / Doutor em Fisiopatologia Medica
24

Follow-Up in Carriers of the ‘MELAS’ Mutation without Strokes

Damian, Maxwell Simon, Hertel, Andreas, Seibel, Peter, Reichmann, Heinz, Bachmann, Georg, Schachenmayr, Walter, Hoer, Gustav, Dorndorf, Wolfgang January 1998 (has links)
Eight carriers of the A3243G mutation of mitochondrial DNA without stroke-like episodes were monitored for up to 7 years in clinical and metabolic studies, by magnetic resonance imaging (MRI) and positron emission tomography (PET). None developed mitochondrial encephalopathy (MELAS), but 2 developed diabetes mellitus, 1 terminal kidney failure and 2 cardiomyopathy. One patient improved markedly under ubiquinone. Electroencephalography showed progressive slowing in 2 cases, but electrophysiological tests and MRI were otherwise noncontributary. PET showed widespread cortical and basal ganglion metabolic deficits in 6 cases. We conclude that internal medical complications are more common than MELAS in adult carriers of the mutation. PET findings, firstly reported in such patients, suggest that chronic subclinical encephalopathy is very frequent, and PET may play a role in monitoring in the future. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
25

Ketogenic Diet Treatment of Defects in the Mitochondrial Malate Aspartate Shuttle and Pyruvate Carrier

Bölsterli, Bigna K., Boltshauser, Eugen, Palmieri, Luigi, Spenger, Johannes, Brunner-Krainz, Michaela, Distelmaier, Felix, Freisinger, Peter, Geis, Tobias, Gropman, Andrea L., Häberle, Johannes, Hentschel, Julia, Jeandidier, Bruno, Karall, Daniela, Keren, Boris, Klabunde-Cherwon, Annick, Konstantopoulou, Vassiliki, Kottke, Raimund, Lasorsa, Francesco M., Makowski, Christine, Mignot, Cyril, O'Gorman Tuura, Ruth, Porcelli, Vito, Santer, René, Sen, Kuntal, Steinbrücker, Katja, Syrbe, Steffen, Wagner, Matias, Ziegler, Andreas, Zöggeler, Thomas, Mayr, Johannes A., Prokisch, Holger, Wortmann, Saskia B. 07 December 2023 (has links)
Themitochondrialmalate aspartate shuttle system(MAS)maintains the cytosolicNAD+/NADH redox balance, thereby sustaining cytosolic redox-dependent pathways, such as glycolysis and serine biosynthesis. Human disease has been associated with defects in four MAS-proteins (encoded by MDH1, MDH2, GOT2, SLC25A12) sharing a neurological/epileptic phenotype, as well as citrin deficiency (SLC25A13) with a complex hepatopathic-neuropsychiatric phenotype. Ketogenic diets (KD) are high-fat/low-carbohydrate diets, which decrease glycolysis thus bypassing the mentioned defects. The same holds for mitochondrial pyruvate carrier (MPC) 1 deficiency, which also presents neurological deficits. We here describe 40 (18 previously unreported) subjects with MAS-/MPC1-defects (32 neurological phenotypes, eight citrin deficiency), describe and discuss their phenotypes and genotypes (presenting 12 novel variants), and the efficacy of KD. Of 13 MAS/MPC1- individuals with a neurological phenotype treated with KD, 11 experienced benefits—mainly a striking effect against seizures. Two individuals with citrin deficiency deceased before the correct diagnosis was established, presumably due to high-carbohydrate treatment. Six citrin-deficient individuals received a carbohydrate-restricted/fat-enriched diet and showed normalisation of laboratory values/hepatopathy as well as age-adequate thriving. We conclude that patients with MAS-/MPC1- defects are amenable to dietary intervention and that early (genetic) diagnosis is key for initiation of proper treatment and can even be lifesaving.
26

Utilisation du modèle levure pour la recherche de voies thérapeutiques contre le syndrome de Barth / Exploration of potential therapeutic pathways against the Barth syndrome using yeast as a model

De Taffin de Tilques, Maxence 15 December 2017 (has links)
Les cardiolipines (CL) sont des phospholipides possédant de nombreux rôles dans la structure et le fonctionnement des mitochondries. Elles sont, par exemple, impliquées dans la stabilisation des complexes des oxydations phosphorylantes, la fusion/fission des membranes mitochondriales, l’import de protéines mitochondriales, la biogénèse des centres fer-soufre (Fe-S), l’apoptose, la protection des mitochondries contre le stress oxydatif…L’ensemble de ces fonctions nécessitent que les chaînes d’acides gras de la CL soient majoritairement insaturées. Le maintien de cette composition en chaînes insaturées requiert une activité acyltransférase portée par la protéine tafazzine, qui est codée par le gène nucléaire TAZ. Des mutations dans ce gène sont la cause du syndrome de Barth (BTHS), qui se caractérise notamment par des myopathies cardiaques et squelettiques, une neutropénie (responsable de nombreuses infections) et des défauts de la chaîne respiratoire. Malgré des progrès considérables dans la compréhension des mécanismes conduisant à la pathogénicité, il n’existe toujours aucune thérapie pour traiter cette maladie. Nous avons donc utilisé la levure Saccharomyces cerevisiae, chez qui la voie de remodelage des CL par la tafazzine est bien conservée, pour modéliser le BTHS et, ainsi non seulement étudier les mécanismes moléculaires sous-jacents de cette maladie, mais aussi identifier différentes voies thérapeutiques potentielles (suppresseurs génétiques et molécules pharmacologiques). Nous avons tout d’abord construit une levure délétée pour le gène orthologue TAZ (TAZ1 chez la levure), la souche Δtaz1. En accord avec des études précédentes, la souche Δtaz1 présente une diminution quantitative de la CL accompagnée d’un changement qualitatif des chaînes d’acides gras1,2 (plus d’acides gras saturés et moins d’insaturés). Nous montrons aussi que cette levure mutante a un défaut de croissance en milieu respiratoire à température élevée (36°C) ainsi que des défauts dans plusieurs composants impliqués dans les oxydations phosphorylantes2. De façon intéressante, alors que le défaut primaire (diminution des CL et changement qualitatif des chaines d’acide gras) est toujours présent, nous montrons que les oxydations phosphorylantes sont restaurées dans la souche Δtaz1 surexprimant Odc1p2, un transporteur mitochondrial d’intermédiaires du cycle de Krebs, ou par plusieurs composés chimiques. Plusieurs de ces drogues sauvant le mutant, dont la cycloheximide, sont des inhibiteurs partiels de la synthèse protéique cytosolique. Cet effet a été confirmé génétiquement par des mutations affectant les ribosomes cytosoliques. L’ensemble des résultats suggère qu’un défaut au niveau des CL provoquerait un stress protéostatique probablement impliqué dans le processus pathologique. / The phospholipid cardiolipin (CL) has many roles in mitochondrial structure and function, ranging from assembly/stability and functioning of the oxidative phosphorylation (OXPHOS) system, fusion and fission of mitochondrial membranes, mitochondrial protein import, iron-sulfur (Fe-S) biogenesis, apoptosis, and protection of mitochondria against oxidative damage. The maintenance of a proper unsaturated acyl chain composition of CL involves the acyltransferase tafazzin in which mutations cause Barth syndrome (BTHS), resulting in cardiac and skeletal myopathy, cyclic neutropenia and respiratory chain defects. Despite considerable progress in the understanding of the underlying pathogenic mechanisms, there are still no effective therapies to treat this disease. We are using the yeast Saccharomyces cerevisiae, in which the tafazzin-based cardiolipin remodeling pathway is conserved, as a model system for the exploration of potential therapeutic pathways against BTHS, by way of genetic suppressors and chemical screening. We first constructed a yeast strain lacking the orthologous taffazin gene (Δtaz1). Consistent with previous studies, our Δtaz1 yeast failed to grow on non-fermentable carbon sources at elevated temperatures (36°C) and exhibited defects in several components of the mitochondrial respiratory system. Interestingly, we found that oxidative phosphorylation was fully restored in Δtaz1 yeast by overexpressing Odc1p [1]-a mitochondrial carrier that transports Krebs cycle intermediates- and by a number of chemical compounds. Some of the rescuing drugs, especially cycloheximide, act by partially inhibiting cytosolic protein synthesis leading to a full recovery of oxidative phosphorylations. Our findings identify potential cellular components and pathways for the pharmacological treatment of BTHS patients.
27

Mitochondrial DNA sequence variation in Finnish patients with maternally inherited type 2 diabetes, epilepsy and mitochondrial disease: risk and novel mutations

Soini, H. (Heidi) 25 November 2013 (has links)
Abstract Cellular energy is produced by the mitochondria via oxidative phosphorylation. In addition to nuclear DNA; the mitochondrion contains circular mitochondrial DNA (mtDNA) molecules. MtDNA is maternally inherited and encodes 37 genes that are crucial for the energy production of the cell. Mutations in the mtDNA cause mitochondrial diseases that manifest as maternally inherited energy metabolism disorders. Common symptoms include diabetes mellitus, myopathy, sensorineural hearing impairment, eye and vision problems, epilepsy and brain manifestations (encephalopathy). Mitochondrial mutations are often heteroplasmic; cells and tissues contain a mix of healthy and mutated mtDNA. The percentage of mutated mtDNA contributes to the severity of symptoms. Mitochondrial DNA also contains numerous polymorphisms; some of which have been reported to be non-neutral, thus contributing to the occurrence of common diseases. Whole mtDNA sequences were obtained from patients with diabetes mellitus (64), epilepsy (79) and unknown mitochondrial disease (66) using conformation-sensitive gel electrophoresis and direct sequencing. Whole mtDNA sequences of a Finnish family with ataxia were also obtained. Restriction fragment length analysis and cloning were used for heteroplasmy quantification. Whole mitochondrial genomes were organized into phylogenetic trees. All nonsynonymous mutations were analyzed with pathogenicity predicting algorithms (SNAP, PolyPhen-2, PMut, SIFT Blink). Non-neutral risk mutations were identified in diabetes mellitus and epilepsy patients. These patients had maternal relatives with diabetes, epilepsy and/or sensorineural hearing impairment. M. 3010A>G and m.16189T>C were found in increased frequency in diabetics and the haplogroup U5b variant m.15218A>G was detected more often among patients with epilepsy. These mutations were predicted to be deleterious in effect. Mitochondrial haplogroup V was found in increased frequency in matrilineal diabetes mellitus patients. We identified an m.8993T>C mutation in a Finnish family with ataxia. This mutation caused an adult-onset ataxic phenotype; previous studies have reported only juvenile onset phenotypes. Novel and rare mtDNA mutations were discovered in patients with an unspecified mitochondrial disease phenotype; these included an insertion m.7585insT and a novel MTTT mutation m. 15933G>A. This thesis emphasizes the importance of full mtDNA sequencing in patients with a suspected mitochondrial disease; novel mutations remain undetected if only the most common mutations are screened. In addition, the increasing importance of non-neutral mtDNA risk variants is supported by the findings of this thesis. In the future, individualized genetics and information on personal risk alleles will become even more important for maintaining health on a personal level. / Tiivistelmä Mitokondriot ovat energiaa tuottavia soluelimiä. Mitokondrioissa on oma rengasmainen mitokondriaalinen DNA (mtDNA), joka esiintyy solussa useana kopiona. MtDNA periytyy vain äidin kautta, joten kaikille lapsille periytyy sama mitokondriaalinen DNA. MtDNA koodaa 37:ää geeniä, jotka ovat tärkeitä solun energiantuotannolle. Geenimuutos mtDNA:ssa voi aiheuttaa äidiltä periytyvän mitokondriotaudin. Mitokondriotaudit ovat energia-aineenvaihdunnan sairauksia, joissa tavallisia oireita ovat diabetes mellitus, lihasoireet (esimerkiksi lihasten ennenaikainen väsymys, myopatia), sydänlihasoireet, maksaoireet, silmä- ja näköoireet, aistimistyyppinen kuulovika sekä aivo-oireet, kuten epilepsia. Oireet vaihtelevat huomattavasti, ja sama mutaatio voi aiheuttaa hyvin erilaisia taudinkuvia. Vakavimmillaan mitokondriotauti voi johtaa kuolemaan jo varhaislapsuudessa. Mutaation prosenttiosuus eli heteroplasmia-aste on usein oireiden vakavuutta määrittelevä tekijä. Mitokondriaalinen DNA muuntuu nopeasti evoluution aikana, joten siinä esiintyy paljon normaalia vaihtelua (polymorfioita). Osa näistä polymorfioista on kuitenkin todettu lievästi haitallisiksi, ja ne lisäävät riskiä sairastua kansanterveydellisesti yleisiin sairauksiin, kuten diabetekseen. Kartoitimme koko mitokondriogenomin muutokset eri potilasryhmiltä, joihin kuului diabetesta, epilepsiaa ja ataksiaa sairastavia potilaita. Lisäksi tutkittiin potilaita, joilla epäiltiin mitokondriotautia. Keskeiset käytetyt menetelmät olivat DNA:n rakenteellisia muutoksia havaitseva geelielektroforeesi ja sekvensointi. Määritimme heteroplasmian käyttäen restriktioentsyymianalyysia sekä kloonausta bakteerisoluihin. Järjestimme potilaiden mtDNA-sekvenssit fylogeneettisiksi puiksi ja kaikki proteiinin koodausta muuttavat geenimuutokset analysoimme haitallisuutta ennustavilla tietokoneohjelmilla (SNAP, PolyPhen-2, PMut, SIFT BLink). Diabetesta sairastavilla potilailla, joilla myös äidinpuoleisessa suvussa esiintyy diabetesta, havaitsimme useammin m.3010A>G- ja m.16189T>C-geenimuutoksia kuin väestöllä keskimäärin. Tutkimustulos tukee aikaisemmin julkaistuja tutkimustuloksia m.16189T>C-geenimuutoksen haitallisuudesta. Epilepsiapotilailta löytyi m.15218A>G-geenimuutos kahdessa U5a1-haploryhmän alatyypissä. Patogeenisyysanalyysien mukaan nämä geenimuutokset olivat haitallisia. Mitokondriaalinen haploryhmä V havaittiin useammin diabetesta sairastavilla kuin terveillä henkilöillä. Tutkimukseen valittiin potilaita, joiden äidinpuoleisilla lähisukulaisilla esiintyi yhtä tai useampaa seuraavista: diabetes, epilepsia tai aistimistyyppinen kuulovika. Väitöstutkimuksessa todetaan lisäksi, että m.8993T>C-mutaatio aiheuttaa aikuisiällä alkavaa ataksia-oireistoa. Kyseinen mutaatio on aiemmin yhdistetty vain lapsuusiän taudinkuviin. Kuvasimme uuden insertiomutaation (m.7585insT) kardiomyopatiasuvussa sekä uuden MTTT-geenin mutaation (m.15933G>A) tuntematonta mitokondriotautia sairastavalla potilaalla. Väitöskirjatutkimuksen tulokset osoittavat, että on tärkeää tutkia koko mitokondriogenomi, kun kyseessä on tuntemattomaksi jäänyt mitokondriaalinen taudinkuva. Uudet, tautia aiheuttavat, mtDNA:n geenimuutokset voivat jäädä tunnistamatta, jos tutkitaan ainoastaan raportoidut, tunnetut, mutaatiot. Lisäksi voi todeta, että mitokondriogenomissa esiintyy lievästi haitallisia geenimuutoksia tai niiden yhdistelmiä, jotka saattavat lisätä riskiä sairastua kansanterveydellisesti merkittäviin sairauksiin, kuten diabetekseen.

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