25 results on '"Turnbull, Douglass M."'
Search Results
2. Detection of Mitochondrial DNA Variation in Human Cells.
- Author
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Krishnan, Kim J., Blackwood, John K., Reeve, Amy K., Turnbull, Douglass M., and Taylor, Robert W.
- Published
- 2010
- Full Text
- View/download PDF
3. The Use of PNAs and Their Derivatives in Mitochondrial Gene Therapy.
- Author
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Janson, Christopher G., During, Matthew J., Smith, Paul M., Ross, Günther F., Wardell, Theresa M., Taylor, Robert W., Turnbull, Douglass M., and Lightowlers, Robert N.
- Abstract
Human mitochondria contain their own genome, mtDNA. This small molecule encodes 24 RNA species and 13 polypeptides, which are essential components of the mitochondrial respiratory chain. The mitochondrial genome is present in hundreds or thousands of copies in each cell and is believed to turnover throughout the life of the cell. Defects of the mitochondrial genome (mtDNA) cause a variety of multisystemic disorders routinely affecting the muscle and nervous system. There is currently no effective treatment for patients with defects of the mitochondrial genome. In many patients, defective cells harbour two sub-populations of mtDNA (a situation termed heteroplasmy), one being normal, the other containing the pathogenic mutation. The mutated copy is often recessive, with biochemical and clinical defects only becoming apparent when the levels of mutated mtDNA outweigh the normal copies. It has therefore been postulated that by selectively preventing replication of the mutated mtDNA, the normal copy will propagate, restoring biochemical function. The search has therefore been on during recent years to identify an antigenomic molecule that will fulfil this criterion. Following evidence that peptide nucleic acids could selectively inhibit replication of templates carrying a known pathogenic mtDNA mutation in vitro, we report on the progress of this approach and the various modifications that are now being used to improve the efficacy of PNA-based antigenomic inhibition. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
4. Clinical Diagnosis of Oxidative Phosphorylation Disorders.
- Author
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Smeitink, Jan A. M., Sengers, Rob C. A., Trijbels, J. M. Frans, McFarland, Robert, Chinnery, Patrick F., Taylor, Robert W., Schaefer, Andrew M., and Turnbull, Douglass M.
- Abstract
Oxidative phosphorylation defects are a common group of inborn errors of metabo lism. Patients may present to a variety of different physicians and at any age. Whilst some patients present with a characteristic phenotype that allows early diagnosis, in many the clinical features are suggestive rather than diagnostic. Neurological features are often prominent in all age groups, but the involvement may be diffuse or remarkable specific (for example optic atrophy alone). In other patients, involvement of other systems is more prominent and in some there is evidence of multiorgan failure. Clinical investigations such as imaging, cardiac studies, and endocrine investigations are often supportive of a diagnosis and form an important part of the clinical investigation. The clinical diagnosis of defects of oxidative phosphorylation is likely to remain a challenge with only the alert clinician identifying the difficult cases. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
5. Analysis of Mitochondrial DNA Mutations.
- Author
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Walker, John M., Barnett, Yvonne A., Barnett, Christopher R., Taylor, Robert W., Andrews, Richard M., Chinnery, Patrick F., and Turnbull, Douglass M.
- Abstract
Since the first demonstration that mutations of the mitochondrial genome were associated with human disease, more than 100 pathological mitochondrial DNA (mtDNA) defects have been characterized in patients with a broad spectrum of clinical manifestations (1). Single-point mutations, involving either protein-encoding genes or more commonly RNA (rRNA and tRNA) genes, represent a substantial proportion (more than one third) of the pathogenic mtDNA mutations described in the literature, and this number is steadily increasing (2, 3). Although some of the more common mtDNA point mutations can be screened using simple polymerase chain reaction (PCR)-based techniques (e.g., restriction digest analysis), an increasing number of pathological point mutations are identified only when large-scale sequencing of either all 22 tRNA genes or the whole mitochondrial genome is performed (4-7). [ABSTRACT FROM AUTHOR]
- Published
- 2000
- Full Text
- View/download PDF
6. Therapeutic potential of somatic cell nuclear transfer for degenerative disease caused by mitochondrial DNA mutations.
- Author
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Greggains, Gareth D., Lister, Lisa M., Tuppen, Helen A. L., Zhang, Qi, Needham, Louise H., Prathalingam, Nilendran, Hyslop, Louise A., Craven, Lyndsey, Polanski, Zbigniew, Murdoch, Alison P., Turnbull, Douglass M., and Herbert, Mary
- Subjects
SOMATIC cells ,INDUCED pluripotent stem cells ,DEGENERATION (Pathology) ,MITOCHONDRIAL DNA ,EMBRYONIC stem cells ,OVUM - Abstract
Induced pluripotent stem cells (iPSCs) hold much promise in the quest for personalised cell therapies. However, the persistence of founder cell mitochondrial DNA (mtDNA) mutations limits the potential of iPSCs in the development of treatments for mtDNA disease. This problem may be overcome by using oocytes containing healthy mtDNA, to induce somatic cell nuclear reprogramming. However, the extent to which somatic cell mtDNA persists following fusion with human oocytes is unknown. Here we show that human nuclear transfer (NT) embryos contain very low levels of somatic cell mtDNA. In light of a recent report that embryonic stem cells can be derived from human NT embryos, our results highlight the therapeutic potential of NT for mtDNA disease, and underscore the importance of using human oocytes to pursue this goal. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
7. Characterization of mtDNA variation in a cohort of South African paediatric patients with mitochondrial disease.
- Author
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van der Walt, Elizna M, Smuts, Izelle, Taylor, Robert W, Elson, Joanna L, Turnbull, Douglass M, Louw, Roan, and van der Westhuizen, Francois H
- Subjects
MITOCHONDRIAL pathology ,GENETIC mutation ,MITOCHONDRIAL DNA ,NUCLEIC acids ,NUCLEOTIDES - Abstract
Mitochondrial disease can be attributed to both mitochondrial and nuclear gene mutations. It has a heterogeneous clinical and biochemical profile, which is compounded by the diversity of the genetic background. Disease-based epidemiological information has expanded significantly in recent decades, but little information is known that clarifies the aetiology in African patients. The aim of this study was to investigate mitochondrial DNA variation and pathogenic mutations in the muscle of diagnosed paediatric patients from South Africa. A cohort of 71 South African paediatric patients was included and a high-throughput nucleotide sequencing approach was used to sequence full-length muscle mtDNA. The average coverage of the mtDNA genome was 81±26 per position. After assigning haplogroups, it was determined that although the nature of non-haplogroup-defining variants was similar in African and non-African haplogroup patients, the number of substitutions were significantly higher in African patients. We describe previously reported disease-associated and novel variants in this cohort. We observed a general lack of commonly reported syndrome-associated mutations, which supports clinical observations and confirms general observations in African patients when using single mutation screening strategies based on (predominantly non-African) mtDNA disease-based information. It is finally concluded that this first extensive report on muscle mtDNA sequences in African paediatric patients highlights the need for a full-length mtDNA sequencing strategy, which applies to all populations where specific mutations is not present. This, in addition to nuclear DNA gene mutation and pathogenicity evaluations, will be required to better unravel the aetiology of these disorders in African patients. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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- View/download PDF
8. Maternally inherited mitochondrial DNA disease in consanguineous families.
- Author
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Alston, Charlotte L, He, Langping, Morris, Andrew A, Hughes, Imelda, Goede, Christian de, Turnbull, Douglass M, McFarland, Robert, and Taylor, Robert W
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MITOCHONDRIAL DNA abnormalities ,PREGNANCY complications ,INBORN errors of metabolism ,GENETIC mutation ,CONSANGUINITY - Abstract
Mitochondrial respiratory chain disease represents one of the most common inborn errors of metabolism and is genetically heterogeneous, with biochemical defects arising from mutations in the mitochondrial genome (mtDNA) or the nuclear genome. As such, inheritance of mitochondrial respiratory chain disease can either follow dominant or recessive autosomal (Mendelian) inheritance patterns, the strictly matrilineal inheritance observed with mtDNA point mutations or X-linked inheritance. Parental consanguinity in respiratory chain disease is often assumed to infer an autosomal recessive inheritance pattern, and the analysis of mtDNA may be overlooked in the pursuit of a presumed nuclear genetic defect. We report the histochemical, biochemical and molecular genetic investigations of two patients with suspected mitochondrial disease who, despite being born to consanguineous first-cousin parents, were found to harbour well-characterised pathogenic mtDNA mutations, both of which were maternally transmitted. Our findings highlight that any diagnostic algorithm for the investigation of mitochondrial respiratory chain disease must include a full and complete analysis of the entire coding sequence of the mitochondrial genome in a clinically relevant tissue. An autosomal basis for respiratory chain disease should not be assumed in consanguineous families and that 'maternally inherited consanguineous' mitochondrial disease may thus be going undiagnosed. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
9. Respiratory chain complex I deficiency caused by mitochondrial DNA mutations.
- Author
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Swalwell, Helen, Kirby, Denise M., Blakely, Emma L., Mitchell, Anna, Salemi, Renato, Sugiana, Canny, Compton, Alison G., Tucker, Elena J, Ke, Bi-Xia, Lamont, Phillipa J., Turnbull, Douglass M, McFarland, Robert, Taylor, Robert W., and Thorburn, David R.
- Subjects
MITOCHONDRIAL DNA abnormalities ,RESPIRATORY diseases ,DNA ,GENETIC mutation ,GENETIC disorders in children ,GENOMES ,CELL fusion - Abstract
Defects of the mitochondrial respiratory chain are associated with a diverse spectrum of clinical phenotypes, and may be caused by mutations in either the nuclear or the mitochondrial genome (mitochondrial DNA (mtDNA)). Isolated complex I deficiency is the most common enzyme defect in mitochondrial disorders, particularly in children in whom family history is often consistent with sporadic or autosomal recessive inheritance, implicating a nuclear genetic cause. In contrast, although a number of recurrent, pathogenic mtDNA mutations have been described, historically, these have been perceived as rare causes of paediatric complex I deficiency. We reviewed the clinical and genetic findings in a large cohort of 109 paediatric patients with isolated complex I deficiency from 101 families. Pathogenic mtDNA mutations were found in 29 of 101 probands (29%), 21 in MTND subunit genes and 8 in mtDNA tRNA genes. Nuclear gene defects were inferred in 38 of 101 (38%) probands based on cell hybrid studies, mtDNA sequencing or mutation analysis (nuclear gene mutations were identified in 22 probands). Leigh or Leigh-like disease was the most common clinical presentation in both mtDNA and nuclear genetic defects. The median age at onset was higher in mtDNA patients (12 months) than in patients with a nuclear gene defect (3 months). However, considerable overlap existed, with onset varying from 0 to >60 months in both groups. Our findings confirm that pathogenic mtDNA mutations are a significant cause of complex I deficiency in children. In the absence of parental consanguinity, we recommend whole mitochondrial genome sequencing as a key approach to elucidate the underlying molecular genetic abnormality. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
10. Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease.
- Author
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Craven, Lyndsey, Tuppen, Helen A., Greggains, Gareth D., Harbottle, Stephen J., Murphy, Julie L., Cree, Lynsey M., Murdoch, Alison P., Chinnery, Patrick F., Taylor, Robert W., Lightowlers, Robert N., Herbert, Mary, and Turnbull, Douglass M.
- Subjects
HUMAN embryos ,MITOCHONDRIAL DNA ,GENETIC mutation ,GENETIC disorders ,ZYGOTES ,BLASTOCYST ,MATERNALLY acquired immunity ,MATERNAL-fetal exchange ,MITOCHONDRIA - Abstract
Mutations in mitochondrial DNA (mtDNA) are a common cause of genetic disease. Pathogenic mutations in mtDNA are detected in approximately 1 in 250 live births and at least 1 in 10,000 adults in the UK are affected by mtDNA disease. Treatment options for patients with mtDNA disease are extremely limited and are predominantly supportive in nature. Mitochondrial DNA is transmitted maternally and it has been proposed that nuclear transfer techniques may be an approach for the prevention of transmission of human mtDNA disease. Here we show that transfer of pronuclei between abnormally fertilized human zygotes results in minimal carry-over of donor zygote mtDNA and is compatible with onward development to the blastocyst stage in vitro. By optimizing the procedure we found the average level of carry-over after transfer of two pronuclei is less than 2.0%, with many of the embryos containing no detectable donor mtDNA. We believe that pronuclear transfer between zygotes, as well as the recently described metaphase II spindle transfer, has the potential to prevent the transmission of mtDNA disease in humans. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
11. A homoplasmic mtDNA variant can influence the phenotype of the pathogenic m.7472Cins MTTS1 mutation: are two mutations better than one?
- Author
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Swalwell, Helen, Blakely, Emma L., Sutton, Ruth, Tonska, Kasia, Elstner, Matthias, Langping He, Taivassalo, Tanja, Burns, Dennis K., Turnbull, Douglass M., Haller, Ronald G., Davidson, Mercy M., and Taylor, Robert W.
- Subjects
GENETIC mutation ,HETEROGENEITY ,MITOCHONDRIAL DNA ,MUSCLE diseases ,DEAFNESS ,DIABETES - Abstract
Mutations in mitochondrial tRNA (mt-tRNA) genes are well recognized as a common cause of human disease, exhibiting a significant degree of clinical heterogeneity. While these differences are explicable, in part, by differences in the innate pathogenicity of the mutation, its distribution and abundance, other factors, including nuclear genetic background, mitochondrial DNA (mtDNA) haplotype and additional mtDNA mutations may influence the expression of mt-tRNA mutations. We describe the clinical, biochemical and molecular findings in a family with progressive myopathy, deafness and diabetes and striking respiratory chain abnormalities due to a well-characterized heteroplasmic mt-tRNA mutation in the mt-tRNA
Ser(UCN) (MTTS1) gene. In addition to the m.7472Cins mutation, all individuals were homoplasmic for another variant, m.7472A>C, affecting the adjacent nucleotide in the mt-tRNASer(UCN) structure. In addition to available patient tissues, we have analysed transmitochondrial cybrid clones harbouring homoplasmic levels of m.7472A>C and varying levels of the m.7472Cins mutation in an attempt to clarify the precise role of the m.7472A>C transversion in the underlying respiratory chain abnormality. Evidence from both in vivo and in vitro studies demonstrate that the m.7472A>C is able to modify the expression of the m.7472Cins mutation and would suggest that it is not a neutral variant but appears to cause a biochemical defect by itself, confirming that homoplasmic mtDNA variants can modulate the phenotypic expression of pathogenic, heteroplasmic mtDNA mutations.European Journal of Human Genetics (2008) 16, 1265–1274; doi:10.1038/ejhg.2008.65; published online 9 April 2008 [ABSTRACT FROM AUTHOR]- Published
- 2008
- Full Text
- View/download PDF
12. Investigation of the mitochondrial genome in patients with atypical motor neuron disease.
- Author
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Phoenix, Catherine, Taylor, Geoffrey A., Hartley, Judith, Nixon, Hannah, Ince, Paul G., Shaw, Pamela J., Turnbull, Douglass M., and Taylor, Robert W.
- Subjects
MITOCHONDRIA ,GENOMES ,MOTOR neuron diseases ,ETIOLOGY of diseases ,MITOCHONDRIAL DNA ,MITOCHONDRIAL pathology ,HISTOCHEMISTRY - Abstract
The molecular aetiology of many patients with motor neuron disease (MND) remains unknown. Recent evidence of mitochondrial dysfunction, in particular the finding of histochemical abnormalities and pathogenic mitochondrial DNA (mtDNA) mutations, has prompted us to investigate further the role of mtDNA abnormalities in a cohort of thirteen patients with atypical MND presentations by whole mitochondrial genome sequencing. No pathogenic mutations were detected suggesting that inherited mtDNA mutations are not a common cause of atypical MND presentations. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
13. Does the mitochondrial genome play a role in the etiology of Alzheimer’s disease?
- Author
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Elson, Joanna L., Herrnstadt, Corinna, Preston, Gwen, Thal, Leon, Morris, Christopher M., Edwardson, J. A., Beal, M. Flint, Turnbull, Douglass M., and Howell, Neil
- Subjects
MITOCHONDRIAL DNA ,ETIOLOGY of diseases ,ALZHEIMER'S disease ,MEDICAL genetics ,GENOMES ,GENETIC code - Abstract
We report here the analyses of complete mtDNA coding region sequences from more than 270 Alzheimer’s disease (AD) patients and normal controls to determine if inherited mtDNA mutations contribute to the etiology of AD. The AD patients and normal individuals were carefully screened and drawn from two populations of European descent in an effort to avoid spurious effects due to local population anomalies. Overall, there were no significant haplogroup associations in the combined AD and normal control sequence sets. Reduced median network analysis revealed that the AD mtDNA sequences contained a higher number of substitutions in tRNA genes, and that there was an elevated frequency of replacement substitutions in the complex I genes of the control sequences. Analysis of the replacement substitutions indicated that those arising in the AD mtDNAs were no more deleterious, on average, than those in the control mtDNAs. The only evidence for the synergistic action of mutations was the presence of both a rare non-conservative replacement substitution and a tRNA mutation in 2 AD mtDNAs, from a total of 145, whereas such a combination of mutations was not observed in the control sequences. Overall, the results reported here indicate that pathogenic inherited mtDNA mutations do not constitute a major etiological factor in sporadic AD. At most, a small proportion of AD patients carry a pathogenic mtDNA mutation and a small proportion of cognitively normal aged individuals carry a mtDNA mutation that reduces the risk of AD. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
14. LHON/MELAS overlap syndrome associated with a mitochondrial MTND1 gene mutation.
- Author
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Blakely, Emma L., de Silva, Rajith, King, Andrew, Schwarzer, Verena, Harrower, Tim, Dawidek, Gervase, Turnbull, Douglass M., and Taylor, Robert W.
- Subjects
MITOCHONDRIAL DNA ,GENETIC mutation ,GENES ,SYNDROMES ,NEUROPATHY ,MITOCHONDRIAL pathology - Abstract
Pathogenic point mutations in the mitochondrial MTND1 gene have previously been described in association with two distinct clinical phenotypes-Leber hereditary optic neuropathy (LHON) and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Here we report the first heteroplasmic mitochondrial DNA (mtDNA) point mutation (3376G>A) in the MTND1 gene associated with an overlap syndrome comprising the clinical features of both LHON and MELAS. Muscle histochemistry revealed subtle mitochondrial abnormalities, while biochemical analysis showed an isolated complex I deficiency. Our findings serve to highlight the growing importance of mutations in mitochondrial complex I structural genes in MELAS and its associated overlap syndromes.European Journal of Human Genetics (2005) 13, 623-627. doi:10.1038/sj.ejhg.5201363 Published online 12 January 2005 [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
15. Noninvasive diagnosis of the 3243A>G mitochondrial DNA mutation using urinary epithelial cells.
- Author
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Mcdonnell, Martina T., Schaefer, Andrew M., Blakely, Emma L., McFarland, Robert, Chinnery, Patrick F., Turnbull, Douglass M., and Taylor, Robert W.
- Subjects
MITOCHONDRIAL DNA ,DNA ,GENETIC mutation ,EPITHELIAL cells ,URINARY organs ,NONINVASIVE diagnostic tests ,GENETICS ,HUMAN genetics - Abstract
The 3243A>G mutation is one of the most frequently observed mutations of mitochondrial DNA (mtDNA), and is associated with numerous clinical presentations including mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), progressive external ophthalmoplegia (PEO) and diabetes and deafness. The routine diagnosis of the 3243A>G mutation in blood is difficult as mutation levels are known to decrease in this tissue over time, while in some patients it may be absent. We have directly compared the levels of the 3243A>G mutation in skeletal muscle, blood and urinary epithelial cells in 18 patients and observed a striking correlation between the mutation load in postmitotic muscle and urinary epithelium, a mitotic tissue. These data strongly support the use of urinary epithelial cells as the tissue of choice in the noninvasive diagnosis of the 3243A>G mutation.European Journal of Human Genetics (2004) 12, 778-781. doi:10.1038/sj.ejhg.5201216 Published online 16 June 2004 [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
16. Leigh disease associated with a novel mitochondrial DNA ND5 mutation.
- Author
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Taylor, Robert W., Morris, Andrew A.M., Hutchinson, Michael, and Turnbull, Douglass M.
- Subjects
NEURODEGENERATION ,MITOCHONDRIAL DNA ,GENETIC mutation - Abstract
Leigh disease is a genetically heterogeneous, neurodegenerative disorder of childhood that is caused by defects of either the nuclear or mitochondrial genome. Here, we report the molecular genetic findings in a patient with neuropathological hallmarks of Leigh disease and complex I deficiency. Direct sequencing of the seven mitochondrial DNA (mtDNA)-encoded complex I (ND) genes revealed a novel missense mutation (T12706C) in the mitochondrial ND5 gene. The mutation is predicted to change an invariant amino acid in a highly conserved transmembrane helix of the mature polypeptide and was heteroplasmic in both skeletal muscle and cultured skin fibroblasts. The association of the T12706C ND5 mutation with a specific biochemical defect involving complex I is highly suggestive of a pathogenic role for this mutation. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
- View/download PDF
17. Selective inhibition of mutant human mitochondrial DNA replication in vitro by peptide nucleic acids.
- Author
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Taylor, Robert W., Chinnery, Patrick F., Turnbull, Douglass M., and Lightowlers, Robert N.
- Published
- 1997
- Full Text
- View/download PDF
18. Sporadic myopathy and exercise intolerance associated with the mitochondrial 8328G>A tRNALys mutation.
- Author
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Blakely, Emma L., Swalwell, Helen, Petty, Richard K. H., McFarland, Robert, Turnbull, Douglass M., and Taylor, Robert W.
- Subjects
LETTERS to the editor ,MITOCHONDRIAL DNA - Abstract
A letter to the editor that reports a second patient with this mt-tRNA
Lys mutation causing exercise intolerance, proximal muscle weakness and bilateral ptosis.- Published
- 2007
- Full Text
- View/download PDF
19. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease.
- Author
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Bender, Andreas, Krishnan, Kim J., Morris, Christopher M., Taylor, Geoffrey A., Reeve, Amy K., Perry, Robert H., Jaros, Evelyn, Hersheson, Joshua S., Betts, Joanne, Klopstock, Thomas, Taylor, Robert W., and Turnbull, Douglass M.
- Subjects
PARKINSON'S disease ,MITOCHONDRIAL DNA abnormalities ,SUBSTANTIA nigra ,MITOCHONDRIAL pathology ,MEDICAL genetics - Abstract
Here we show that in substantia nigra neurons from both aged controls and individuals with Parkinson disease, there is a high level of deleted mitochondrial DNA (mtDNA) (controls, 43.3% ± 9.3%; individuals with Parkinson disease, 52.3% ± 9.3%). These mtDNA mutations are somatic, with different clonally expanded deletions in individual cells, and high levels of these mutations are associated with respiratory chain deficiency. Our studies suggest that somatic mtDNA deletions are important in the selective neuronal loss observed in brain aging and in Parkinson disease. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
20. Reversal of a mitochondrial DNA defect in human skeletal muscle.
- Author
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Clark, Kim M., Bindoff, Laurence A., Lightowlers, Robert N., Andrews, Richard M., Griffiths, Philip G., Johnson, Margaret A., Brierley, Elizabeth J., and Turnbull, Douglass M.
- Published
- 1997
- Full Text
- View/download PDF
21. Differential diagnosis in ptosis and ophthalmoplegia: mitochondrial disease or myasthenia?
- Author
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Whittaker, Roger G., Schaefer, Andrew M., Taylor, Robert W., and Turnbull, Douglass M.
- Subjects
LETTERS to the editor ,DIFFERENTIAL diagnosis - Abstract
A letter to the editor is presented in response to the article about the differential diagnosis in ptosis and opthalmoplegia.
- Published
- 2007
- Full Text
- View/download PDF
22. A roundabout route to gene therapy.
- Author
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Turnbull, Douglass M. and Lightowlers, Robert N.
- Subjects
- *
MITOCHONDRIAL pathology , *GENE therapy , *GENETIC engineering - Abstract
The uniqueness of the mitochondrial genome presents a number of obstacles to the successful use of gene therapy for the treatment of mitochondrial DNA disease. A new study shows that the effects of a pathogenic mutation in a human mitochondrial gene can be rectified by expressing an engineered wildtype copy of the gene in the nucleus. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
- View/download PDF
23. Multiple neonatal deaths due to a homoplasmic mitochondrial DNA mutation.
- Author
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McFarland, Robert, Clark, Kim M., Morris, Andrew A.M., Taylor, Robert W., Macphail, Sheila, Lightowlers, Robert N., and Turnbull, Douglass M.
- Subjects
GENETIC mutation ,INFANT death ,MITOCHONDRIAL DNA - Abstract
Mutations of mitochondrial DNA (mtDNA) are an important cause of genetic disease. We describe a family with an unusual homoplasmic mutation that resulted in six neonatal deaths and one surviving child with Leigh syndrome. The mother is clinically normal, but a severe biochemical and molecular genetic defect was present in both a fatally affected child and the mother. This family highlights the role of homoplasmic mt-tRNA mutations in genetic disease. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
- View/download PDF
24. Might mammalian mitochondria merge?
- Author
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Turnbull, Douglass M. and Lightowlers, Robert N.
- Subjects
- *
MITOCHONDRIAL DNA , *LABORATORY mice , *TRANSGENIC mice - Abstract
Reports on the development of a transgenic mouse model carrying pathogenic mitochondria DNA. Scarcity of evidence for the dynamic nature of mammalian mitochondria; Background on mitochondrial DNA diseases as a group of genetic disorders.
- Published
- 2001
- Full Text
- View/download PDF
25. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA.
- Author
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Andrews, Richard M., Kubacka, Iwona, Chinnery, Patrick F., Lightowlers, Robert N., Turnbull, Douglass M., and Howell, Neil
- Subjects
MITOCHONDRIAL DNA ,NUCLEOTIDE sequence ,MITOCHONDRIA ,DNA - Abstract
Discusses the reanalysis and revision of the Cambridge reference sequence (CRS) for human mitochondrial DNA. Determination of the complete mitochondrial DNA sequence using a series of 28 overlapping polymerase chain reaction-amplified fragments spanning the entire length of the mitochondrial genome; Resequencing information revealing errors and rare polymorphisms in the CRS.
- Published
- 1999
- Full Text
- View/download PDF
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