Robert W Taylor

Summary

Affiliation: University of Newcastle
Country: UK

Publications

  1. pmc The p.M292T NDUFS2 mutation causes complex I-deficient Leigh syndrome in multiple families
    Helen A L Tuppen
    Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Medical School, Framlington Place, Newcastle upon Tyne, UK
    Brain 133:2952-63. 2010
  2. ncbi request reprint Diagnosis of mitochondrial disease: assessment of mitochondrial DNA heteroplasmy in blood
    R W Taylor
    Department of Neurology, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, United Kingdom
    Biochem Biophys Res Commun 251:883-7. 1998
  3. ncbi request reprint Gene therapy for the treatment of mitochondrial DNA disorders
    Robert W Taylor
    University of Newcastle upon Tyne, Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, Newcastle upon Tyne, NE2 4HH, UK
    Expert Opin Biol Ther 5:183-94. 2005
  4. ncbi request reprint Catastrophic presentation of mitochondrial disease due to a mutation in the tRNA(His) gene
    R W Taylor
    Mitochondrial Research Group, School of Neurology, Neurobiology, and Psychiatry, The Medical School, University of Newcastle upon Tyne, UK
    Neurology 62:1420-3. 2004
  5. ncbi request reprint In-vitro genetic modification of mitochondrial function
    R W Taylor
    Department of Neurology, The Medical School, University of Newcastle upon Tyne, UK
    Hum Reprod 15:79-85. 2000
  6. doi request reprint A homoplasmic mtDNA variant can influence the phenotype of the pathogenic m.7472Cins MTTS1 mutation: are two mutations better than one?
    Helen Swalwell
    Mitochondrial Research Group, The Medical School, Newcastle University, Newcastle upon Tyne, UK
    Eur J Hum Genet 16:1265-74. 2008
  7. ncbi request reprint Prevalence of mitochondrial DNA disease in adults
    Andrew M Schaefer
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, Newcastle University, Newcastle upon Tyne, United Kingdom
    Ann Neurol 63:35-9. 2008
  8. pmc Mitochondrial DNA defects and selective extraocular muscle involvement in CPEO
    Laura C Greaves
    Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom
    Invest Ophthalmol Vis Sci 51:3340-6. 2010
  9. pmc Defects in multiple complexes of the respiratory chain are present in ageing human colonic crypts
    Laura C Greaves
    Mitochondrial Research Group, Institute for Ageing and Health, Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, UK
    Exp Gerontol 45:573-9. 2010
  10. pmc Somatic mitochondrial DNA deletions accumulate to high levels in aging human extraocular muscles
    Patrick Yu-Wai-Man
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom
    Invest Ophthalmol Vis Sci 51:3347-53. 2010

Detail Information

Publications138 found, 100 shown here

  1. pmc The p.M292T NDUFS2 mutation causes complex I-deficient Leigh syndrome in multiple families
    Helen A L Tuppen
    Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Medical School, Framlington Place, Newcastle upon Tyne, UK
    Brain 133:2952-63. 2010
    ..Our results confirm that NDUFS2 is a mutational hotspot in Caucasian children with isolated complex I deficiency and recommend the routine diagnostic investigation of this gene in patients with Leigh or Leigh-like phenotypes...
  2. ncbi request reprint Diagnosis of mitochondrial disease: assessment of mitochondrial DNA heteroplasmy in blood
    R W Taylor
    Department of Neurology, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, United Kingdom
    Biochem Biophys Res Commun 251:883-7. 1998
    ..We believe that mtDNA pseudogenes may therefore present significant difficulties in the accurate identification of pathogenic heteroplasmic mtDNA mutations in blood...
  3. ncbi request reprint Gene therapy for the treatment of mitochondrial DNA disorders
    Robert W Taylor
    University of Newcastle upon Tyne, Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, Newcastle upon Tyne, NE2 4HH, UK
    Expert Opin Biol Ther 5:183-94. 2005
    ....
  4. ncbi request reprint Catastrophic presentation of mitochondrial disease due to a mutation in the tRNA(His) gene
    R W Taylor
    Mitochondrial Research Group, School of Neurology, Neurobiology, and Psychiatry, The Medical School, University of Newcastle upon Tyne, UK
    Neurology 62:1420-3. 2004
    ..This G12147A transition is heteroplasmic, predicted to disrupt a highly conserved base pair, and segregates with the cytochrome c oxidase deficiency in single muscle fibers...
  5. ncbi request reprint In-vitro genetic modification of mitochondrial function
    R W Taylor
    Department of Neurology, The Medical School, University of Newcastle upon Tyne, UK
    Hum Reprod 15:79-85. 2000
    ..The possibilities of extending this strategy to the treatment of mtDNA deletion disorders are discussed...
  6. doi request reprint A homoplasmic mtDNA variant can influence the phenotype of the pathogenic m.7472Cins MTTS1 mutation: are two mutations better than one?
    Helen Swalwell
    Mitochondrial Research Group, The Medical School, Newcastle University, Newcastle upon Tyne, UK
    Eur J Hum Genet 16:1265-74. 2008
    ....
  7. ncbi request reprint Prevalence of mitochondrial DNA disease in adults
    Andrew M Schaefer
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, Newcastle University, Newcastle upon Tyne, United Kingdom
    Ann Neurol 63:35-9. 2008
    ..Consequently, the aim of this study was to accurately define the prevalence of mtDNA disease (primary mutation occurs in mtDNA) in the working-age population of the North East of England...
  8. pmc Mitochondrial DNA defects and selective extraocular muscle involvement in CPEO
    Laura C Greaves
    Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom
    Invest Ophthalmol Vis Sci 51:3340-6. 2010
    ..The data also suggest that tissue-specific mechanisms are involved in the clonal expansion and expression of secondary mtDNA deletions in CPEO patients with nuclear genetic defects...
  9. pmc Defects in multiple complexes of the respiratory chain are present in ageing human colonic crypts
    Laura C Greaves
    Mitochondrial Research Group, Institute for Ageing and Health, Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, UK
    Exp Gerontol 45:573-9. 2010
    ..Finally we discuss the possible mechanisms by which multiple respiratory chain complex defects may occur in these cells...
  10. pmc Somatic mitochondrial DNA deletions accumulate to high levels in aging human extraocular muscles
    Patrick Yu-Wai-Man
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom
    Invest Ophthalmol Vis Sci 51:3347-53. 2010
    ..CONCLUSIONS. The results show an exponential increase in COX deficiency in EOMs beginning in early adulthood, which suggests an accelerated aging process compared with other postmitotic tissues...
  11. doi request reprint The pathogenic m.3243A>T mitochondrial DNA mutation is associated with a variable neurological phenotype
    Charlotte L Alston
    Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne, UK
    Neuromuscul Disord 20:403-6. 2010
    ..3243A>T mutation with COX deficiency...
  12. pmc What is influencing the phenotype of the common homozygous polymerase-γ mutation p.Ala467Thr?
    Vivienne C M Neeve
    Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK
    Brain 135:3614-26. 2012
    ..Our results suggest that the mitochondrial DNA background plays an important role in modifying the disease phenotype but nuclear modifiers, epigenetic and environmental factors may also influence the severity of disease...
  13. ncbi request reprint The m.5650G>A mitochondrial tRNAAla mutation is pathogenic and causes a phenotype of pure myopathy
    Robert McFarland
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, Framlington Place, Newcastle University, Newcastle upon Tyne, England NE2 4HH, UK
    Neuromuscul Disord 18:63-7. 2008
    ..This report is therefore the first description of the phenotype associated solely with this mutation and confirms its pathogenicity...
  14. pmc Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy
    Rita Horvath
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK
    Brain 132:3165-74. 2009
    ..This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis...
  15. doi request reprint POLG mutations cause decreased mitochondrial DNA repopulation rates following induced depletion in human fibroblasts
    Joanna D Stewart
    Mitochondrial Research Group, Institute of Human Genetics, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK
    Biochim Biophys Acta 1812:321-5. 2011
    ....
  16. pmc Disease progression in patients with single, large-scale mitochondrial DNA deletions
    John P Grady
    1 Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
    Brain 137:323-34. 2014
    ....
  17. ncbi request reprint Mutation of the linker region of the polymerase gamma-1 (POLG1) gene associated with progressive external ophthalmoplegia and Parkinsonism
    Gavin Hudson
    Mitochondrial Research Group, University of Newcastle upon Tyne, United Kingdom
    Arch Neurol 64:553-7. 2007
    ..To define the molecular basis of the autosomal dominant progressive external ophthalmoplegia and parkinsonism in a large family with a dominantly transmitted multiple mitochondrial DNA deletion disorder...
  18. ncbi request reprint The UK MRC Mitochondrial Disease Patient Cohort Study: clinical phenotypes associated with the m.3243A>G mutation--implications for diagnosis and management
    Victoria Nesbitt
    Wellcome Trust Centre for Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
    J Neurol Neurosurg Psychiatry 84:936-8. 2013
    ..Many patients affected by this mutation exhibit a clinical phenotype that does not fall within accepted criteria for the currently recognised classical mitochondrial syndromes...
  19. pmc Concentric hypertrophic remodelling and subendocardial dysfunction in mitochondrial DNA point mutation carriers
    Matthew G D Bates
    Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
    Eur Heart J Cardiovasc Imaging 14:650-8. 2013
    ..Screening strategies for cardiac disease are unclear. We investigated whether myocardial abnormalities could be identified in mitochondrial DNA mutation carriers without clinical cardiac involvement...
  20. doi request reprint What causes mitochondrial DNA deletions in human cells?
    Kim J Krishnan
    Mitochondrial Research Group, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
    Nat Genet 40:275-9. 2008
    ..This conclusion has important implications for prevention of mtDNA disease and, potentially, for our understanding of the aging process...
  21. doi request reprint Resistance training in patients with single, large-scale deletions of mitochondrial DNA
    Julie L Murphy
    Mitochondrial Research Group, Newcastle University, Framlington Place, Newcastle upon Tyne, UK
    Brain 131:2832-40. 2008
    ....
  22. ncbi request reprint Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance
    Gavin Hudson
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
    Brain 131:329-37. 2008
    ..This demonstrates the importance of OPA1 in mtDNA maintenance, and implicates OPA1 in diseases associated with secondary defects of mtDNA...
  23. pmc Defining cardiac adaptations and safety of endurance training in patients with m.3243A>G-related mitochondrial disease
    Matthew G D Bates
    Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE2 4HH, UK Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE7 7DN, UK Electronic address
    Int J Cardiol 168:3599-608. 2013
    ..Endurance exercise training improves symptoms and skeletal muscle function, yet cardiac adaptations are unknown...
  24. pmc The low abundance of clonally expanded mitochondrial DNA point mutations in aged substantia nigra neurons
    Amy K Reeve
    Newcastle University Centre for Brain Ageing and Vitality, Institute for Ageing and Health, Newcastle University, UK
    Aging Cell 8:496-8. 2009
    ..This contrasts observations in mitotic tissues and suggests that different forms of mtDNA maintenance may exist in these two cell types...
  25. pmc Comparison of mitochondrial mutation spectra in ageing human colonic epithelium and disease: absence of evidence for purifying selection in somatic mitochondrial DNA point mutations
    Laura C Greaves
    Newcastle University Centre for Brain Ageing and Vitality, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom
    PLoS Genet 8:e1003082. 2012
    ..These data provide little evidence for any selective constraints on the occurrence and expansion of mtDNA mutations in somatic cells of the human colon during human ageing in contrast to germline mutations seen in the general population...
  26. pmc Cytochrome c oxidase-intermediate fibres: importance in understanding the pathogenesis and treatment of mitochondrial myopathy
    Julie L Murphy
    Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, UK
    Neuromuscul Disord 22:690-8. 2012
    ..Assessing changes in intermediate fibres will be crucial to evaluating the responses to treatment and in particular to exercise training regimes in patients with mitochondrial DNA disease...
  27. pmc Microangiopathy in the cerebellum of patients with mitochondrial DNA disease
    Nichola Z Lax
    The Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
    Brain 135:1736-50. 2012
    ..Since therapeutic strategies targeting the central nervous system are limited, modulating vascular function presents an exciting opportunity to lessen the burden of disease in these patients...
  28. ncbi request reprint Familial myopathy: new insights into the T14709C mitochondrial tRNA mutation
    Robert McFarland
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, United Kingdom
    Ann Neurol 55:478-84. 2004
    ..Furthermore, variation in phenotype between homoplasmic individuals implies a crucial contribution from the nuclear genetic environment in determining the clinical outcome of mt-tRNA mutations...
  29. ncbi request reprint Ophthalmoplegia due to mitochondrial DNA disease: the need for genetic diagnosis
    Andrew M Schaefer
    School of Neurology, Neurobiology and Psychiatry, The Medical School, Framlington Place, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom
    Muscle Nerve 32:104-7. 2005
    ..The case serves to illustrate the importance of pursuing the proposed mitochondrial genetic abnormality, even in patients with normal biopsy findings...
  30. doi request reprint The investigation and diagnosis of pathogenic mitochondrial DNA mutations in human urothelial cells
    John K Blackwood
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
    Biochem Biophys Res Commun 393:740-5. 2010
    ..Our results have implications for the diagnosis, management and counselling of families with mtDNA disease...
  31. pmc Pathogenic mitochondrial tRNA point mutations: nine novel mutations affirm their importance as a cause of mitochondrial disease
    Emma L Blakely
    Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
    Hum Mutat 34:1260-8. 2013
    ..5690A>G, m.7451A>T, m.12206C>T, m.12317T>C, and m.16023G>A), whereas the remaining three currently lack sufficient evidence and are therefore classed as 'possibly pathogenic' (m.4289T>C, m.7554G>A, and m.8304G>A)...
  32. ncbi request reprint Near-identical segregation of mtDNA heteroplasmy in blood, muscle, urinary epithelium, and hair follicles in twins with optic atrophy, ptosis, and intractable epilepsy
    Achilles Spyropoulos
    Wellcome Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, England
    JAMA Neurol 70:1552-5. 2013
    ..The phenotypic heterogeneity is partly owing to different percentage levels of mutant mtDNA heteroplasmy in different tissues, but the factors influencing this are poorly understood...
  33. pmc Age-associated mitochondrial DNA mutations lead to small but significant changes in cell proliferation and apoptosis in human colonic crypts
    Marco Nooteboom
    Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
    Aging Cell 9:96-9. 2010
    ..We show for the first time in aging human tissue that RC deficiency attenuates cell proliferation and increases apoptosis in the progeny of RC deficient stem cells, leading to decreased crypt cell population...
  34. pmc Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency
    Charlotte L Alston
    Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Medical School, Newcastle University, Newcastle upon Tyne, UK
    J Med Genet 49:569-77. 2012
    ....
  35. pmc Mutations in the mitochondrial tRNA Ser(AGY) gene are associated with deafness, retinal degeneration, myopathy and epilepsy
    Helen A L Tuppen
    Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
    Eur J Hum Genet 20:897-904. 2012
    ..Our findings expand the spectrum of pathogenic mutations associated with the MTTS2 gene and highlight MTTS2 mutations as an important cause of retinal and syndromic auditory impairment...
  36. pmc Maternally inherited mitochondrial DNA disease in consanguineous families
    Charlotte L Alston
    Mitochondrial Research Group and NCG Mitochondrial Laboratory, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
    Eur J Hum Genet 19:1226-9. 2011
    ..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...
  37. pmc Loss of myelin-associated glycoprotein in kearns-sayre syndrome
    Nichola Z Lax
    Mitochondrial Research Group, Institute for Aging and Health, Newcastle University, Framlington Place, Newcastle upon Tyne, United Kingdom
    Arch Neurol 69:490-9. 2012
    ..To explore myelin components and mitochondrial changes within the central nervous system in patients with well-characterized mitochondrial disorders due to nuclear DNA or mitochondrial DNA (mtDNA) mutations...
  38. ncbi request reprint Changes in the human mitochondrial genome after treatment of malignant disease
    Theresa M Wardell
    Department of Neurology, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK
    Mutat Res 525:19-27. 2003
    ..Our studies have shown that in patients who have been treated for cancer there is an increased level of mtDNA damage...
  39. ncbi request reprint Mitochondrial DNA and disease
    Laura C Greaves
    Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, UK
    J Pathol 226:274-86. 2012
    ....
  40. pmc The prevalence and natural history of dominant optic atrophy due to OPA1 mutations
    Patrick Yu-Wai-Man
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, UK
    Ophthalmology 117:1538-46, 1546.e1. 2010
    ..To define the prevalence and natural history of this optic nerve disorder, we performed a population-based epidemiologic and molecular study of presumed DOA cases in the north of England...
  41. ncbi request reprint A novel sporadic mutation in cytochrome c oxidase subunit II as a cause of rhabdomyolysis
    Robert McFarland
    Mitochondrial Research Group, Department of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, Framlington Place, NE2 4HH, UK
    Neuromuscul Disord 14:162-6. 2004
    ..We believe that this study demonstrates the importance of whole mitochondrial genome sequencing and of access to large sequence databases...
  42. doi request reprint A novel mitochondrial MTND5 frameshift mutation causing isolated complex I deficiency, renal failure and myopathy
    Charlotte L Alston
    Mitochondrial Research Group and NCG Rare Mitochondrial Disorders of Adults and Children Service, Newcastle University, Newcastle upon Tyne, UK
    Neuromuscul Disord 20:131-5. 2010
    ....
  43. pmc Late-onset respiratory failure due to TK2 mutations causing multiple mtDNA deletions
    Charlotte L Alston
    From Newcastle University C L A, A M S, P R, K J K, E L B, L H, K C, R H, D M T, G S G, R W T, Newcastle upon Tyne, UK Karolinska Institute N S, A K, Stockholm, Sweden Hope Hospital M R, Salford and Royal Preston Hospital A V, J N, Preston, UK
    Neurology 81:2051-3. 2013
    ..Mutations in nuclear genes involved in the maintenance of mitochondrial DNA (mtDNA) are associated with an extensive spectrum of clinical phenotypes, manifesting as either mtDNA depletion syndromes or multiple mtDNA deletion disorders.(1.) ..
  44. doi request reprint Neuromuscular disease presentation with three genetic defects involving two genomes
    Mazhor Al-Dosary
    Mitochondrial Research Group and NCG Rare Mitochondrial Disorders of Adults and Children Service, Newcastle University, Newcastle upon Tyne, UK
    Neuromuscul Disord 19:841-4. 2009
    ..Muscle biopsy revealed many COX-deficient fibres which we show contain high levels of a third genetic defect--a novel, mitochondrial tRNA(Leu(CUN)) (MTTL2) gene mutation...
  45. ncbi request reprint Strategies for treating disorders of the mitochondrial genome
    Paul M Smith
    Mitochondrial Research Group, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK
    Biochim Biophys Acta 1659:232-9. 2004
    ..In this article, we present the theory behind several concepts and report progress. We also discuss some of the recent difficulties encountered in the progress towards an antigenomc approach to treating mtDNA disorders...
  46. ncbi request reprint Early-onset cataracts, spastic paraparesis, and ataxia caused by a novel mitochondrial tRNAGlu (MT-TE) gene mutation causing severe complex I deficiency: a clinical, molecular, and neuropathologic study
    Nichola Z Lax
    Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne, UK
    J Neuropathol Exp Neurol 72:164-75. 2013
    ..This study emphasizes the importance of molecular genetic and postmortem neuropathologic analyses for furthering our understanding of underlying mechanisms of mitochondrial disorders...
  47. doi request reprint Pathogenic mitochondrial tRNA mutations--which mutations are inherited and why?
    Joanna L Elson
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
    Hum Mutat 30:E984-92. 2009
    ..This is entirely compatible with recent observations on the mitochondrial genetic bottleneck in early development and has important implications for families with mt-tRNA disease...
  48. pmc Production of transmitochondrial cybrids containing naturally occurring pathogenic mtDNA variants
    Deborah Pye
    Mitochondrial Research Group, University of Newcastle upon Tyne, School of Neurology, Neurobiology and Psychiatry, Framlington Place, Newcastle upon Tyne NE2 4HH, UK
    Nucleic Acids Res 34:e95. 2006
    ..This method can therefore be exploited to produce a library of cell lines carrying pathogenic human mtDNA for further study...
  49. doi request reprint A new mitochondrial transfer RNAPro gene mutation associated with myoclonic epilepsy with ragged-red fibers and other neurological features
    Emma L Blakely
    The Medical School, Newcastle University, Newcastle upon Tyne, Enlgand
    Arch Neurol 66:399-402. 2009
    ..Pathogenic mutations of the human mitochondrial genome are associated with well-characterized, progressive neurological syndromes, with mutations in the transfer RNA genes being particularly prominent...
  50. doi request reprint Novel mutations in the TK2 gene associated with fatal mitochondrial DNA depletion myopathy
    Emma Blakely
    Mitochondrial Research Group, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
    Neuromuscul Disord 18:557-60. 2008
    ..Sequencing of the thymidine kinase 2 (TK2) gene revealed two, novel heterozygous mutations (p.Q87X and p.N100S) with parental DNA analysis confirming the transmission of mutated alleles...
  51. ncbi request reprint A novel mitochondrial DNA tRNA(Ile) (A4267G) mutation in a sporadic patient with mitochondrial myopathy
    Robert W Taylor
    Department of Neurology, The Medical School, University of Newcastle upon Tyne, Framlington Place, NE2 4HH, Newcastle upon Tyne, UK
    Neuromuscul Disord 12:659-664. 2002
    ..Moreover, we were unable to detect the A4267G mutation in lymphocytes, buccal epithelia and hair of the patient's mother and two siblings, implying that the A4267G transition represents a sporadic, germline mutation...
  52. pmc Overexpression of human mitochondrial valyl tRNA synthetase can partially restore levels of cognate mt-tRNAVal carrying the pathogenic C25U mutation
    Joanna Rorbach
    Mitochondrial Research Group, Institute of Neuroscience, Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK
    Nucleic Acids Res 36:3065-74. 2008
    ..These data indicate that variations in the levels of VARS2L between tissue types and patients could underlie the difference in clinical presentation between individuals homoplasmic for the 1624C>T mutation...
  53. doi request reprint Long-term survival of neonatal mitochondrial complex III deficiency associated with a novel BCS1L gene mutation
    Helen A L Tuppen
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
    Mol Genet Metab 100:345-8. 2010
    ..Our data indicate that BCS1L mutations can cause a variable, neurological course which is not always fatal in childhood...
  54. pmc Respiratory chain complex I deficiency caused by mitochondrial DNA mutations
    Helen Swalwell
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne, UK
    Eur J Hum Genet 19:769-75. 2011
    ..In the absence of parental consanguinity, we recommend whole mitochondrial genome sequencing as a key approach to elucidate the underlying molecular genetic abnormality...
  55. ncbi request reprint Noninvasive diagnosis of the 3243A > G mitochondrial DNA mutation using urinary epithelial cells
    Martina T McDonnell
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, UK
    Eur J Hum Genet 12:778-81. 2004
    ..These data strongly support the use of urinary epithelial cells as the tissue of choice in the noninvasive diagnosis of the 3243A > G mutation...
  56. ncbi request reprint Sporadic mitochondrial myopathy due to a new mutation in the mitochondrial tRNASer(UCN) gene
    Seyed Bidooki
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK
    Neuromuscul Disord 14:417-20. 2004
    ..This is the eighth disease-causing mutation in this tRNA gene and confirms serine (UCN) as one of the most common sites for mtDNA mutation...
  57. pmc Mutation of the human mitochondrial phenylalanine-tRNA synthetase causes infantile-onset epilepsy and cytochrome c oxidase deficiency
    Abdulraheem Almalki
    Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE2 4HH, UK Electronic address
    Biochim Biophys Acta 1842:56-64. 2014
    ..Asp325Tyr mutation is pathogenic, causing respiratory chain deficiency and neurological deficits on account of defective aminoacylation of mt-tRNA(Phe). ..
  58. ncbi request reprint LHON/MELAS overlap syndrome associated with a mitochondrial MTND1 gene mutation
    Emma L Blakely
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, University of Newcastle upon Tyne, UK
    Eur J Hum Genet 13:623-7. 2005
    ..Our findings serve to highlight the growing importance of mutations in mitochondrial complex I structural genes in MELAS and its associated overlap syndromes...
  59. ncbi request reprint Sporadic intragenic inversion of the mitochondrial DNA MTND1 gene causing fatal infantile lactic acidosis
    Emma L Blakely
    Mitochindrial Research Group, School of Neurlogy, Neurobiology and Psychiatry, The University of Newcastle upon Tyne, UK
    Pediatr Res 59:440-4. 2006
    ..Our report highlights the enormous phenotypic diversity that exists among pathogenic mtDNA mutations and reemphasizes the need for appropriate genetic counseling for families affected by mtDNA disease...
  60. ncbi request reprint De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency
    Robert McFarland
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, University of Newcastle upon Tyne, United Kingdom
    Ann Neurol 55:58-64. 2004
    ..Mitochondrial DNA disease may be considerably more prevalent in the pediatric population than currently predicted and should be considered in patients with infantile mitochondrial encephalopathies and complex I deficiency...
  61. pmc The m.3291T>C mt-tRNA(Leu(UUR)) mutation is definitely pathogenic and causes multisystem mitochondrial disease
    John W Yarham
    Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom
    J Neurol Sci 325:165-9. 2013
    ....
  62. pmc Sensory neuronopathy in patients harbouring recessive polymerase γ mutations
    Nichola Z Lax
    Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK
    Brain 135:62-71. 2012
    ....
  63. doi request reprint A comparative analysis approach to determining the pathogenicity of mitochondrial tRNA mutations
    John W Yarham
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, UK
    Hum Mutat 32:1319-25. 2011
    ....
  64. ncbi request reprint Diabetes and deafness: is it sufficient to screen for the mitochondrial 3243A>G mutation alone?
    Roger G Whittaker
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, Newcastle University, Newcastle upon Tyne, UK
    Diabetes Care 30:2238-9. 2007
  65. ncbi request reprint A multiplex real-time PCR method to detect and quantify mitochondrial DNA deletions in individual cells
    Kim J Krishnan
    Mitochondrial Research Group, School of Neurology, Neurobiology, and Psychiatry, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
    Anal Biochem 370:127-9. 2007
  66. ncbi request reprint The diagnosis of mitochondrial muscle disease
    Robert W Taylor
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK
    Neuromuscul Disord 14:237-45. 2004
    ..Here, we describe a step-by-step approach to the clinical and laboratory diagnosis of mitochondrial muscle disease, highlighting the many potential problems that can hinder reaching the correct diagnosis...
  67. ncbi request reprint Investigation of the mitochondrial genome in patients with atypical motor neuron disease
    Catherine Phoenix
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle, Newcastle NE2 4HH, UK
    J Neurol 254:482-7. 2007
    ..No pathogenic mutations were detected suggesting that inherited mtDNA mutations are not a common cause of atypical MND presentations...
  68. ncbi request reprint Genotypes from patients indicate no paternal mitochondrial DNA contribution
    Robert W Taylor
    School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
    Ann Neurol 54:521-4. 2003
    ..Our findings suggest that paternal transmission of mtDNA is rare and should not alter our genetic advice to families...
  69. pmc Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission
    Laura C Greaves
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom
    Proc Natl Acad Sci U S A 103:714-9. 2006
    ..This has important implications for the biology of the normal adult human colon and possibly for the growth and spread of colorectal neoplasms...
  70. ncbi request reprint A mitochondrial cytochrome b mutation causing severe respiratory chain enzyme deficiency in humans and yeast
    Emma L Blakely
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, UK
    FEBS J 272:3583-92. 2005
    ..Biochemical studies of the equivalent amino-acid substitution (Lys319Pro) in the yeast enzyme showed a loss of enzyme activity and decrease in the steady-state level of bc1 complex in the mutant confirming pathogenicity...
  71. doi request reprint Detection of mitochondrial DNA variation in human cells
    Kim J Krishnan
    Mitochondrial Research Group, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK
    Methods Mol Biol 628:227-57. 2010
    ....
  72. pmc MPV17 mutation causes neuropathy and leukoencephalopathy with multiple mtDNA deletions in muscle
    Emma L Blakely
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
    Neuromuscul Disord 22:587-91. 2012
    ..The mpv17 protein is therefore intimately involved in both the mtDNA replication and repair processes and associated with both quantitative and qualitative mtDNA abnormalities...
  73. ncbi request reprint The clinical spectrum of the m.10191T>C mutation in complex I-deficient Leigh syndrome
    Victoria Nesbitt
    Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
    Dev Med Child Neurol 54:500-6. 2012
    ....
  74. doi request reprint A novel mitochondrial tRNAGlu (MTTE) gene mutation causing chronic progressive external ophthalmoplegia at low levels of heteroplasmy in muscle
    Charlotte L Alston
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK
    J Neurol Sci 298:140-4. 2010
    ....
  75. pmc Nuclear factors involved in mitochondrial translation cause a subgroup of combined respiratory chain deficiency
    John P Kemp
    Mitochondrial Research Group, Institute of Human Genetics, Newcastle University, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK
    Brain 134:183-95. 2011
    ....
  76. ncbi request reprint A homoplasmic mitochondrial transfer ribonucleic acid mutation as a cause of maternally inherited hypertrophic cardiomyopathy
    Robert W Taylor
    Department of Neurology, The Medical School, Framlington Place, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK
    J Am Coll Cardiol 41:1786-96. 2003
    ..The purpose of this study was to understand the clinical and molecular features of familial hypertrophic cardiomyopathy (HCM) in which a mitochondrial abnormality was strongly suspected...
  77. ncbi request reprint Motor neuron disease in a patient with a mitochondrial tRNAIle mutation
    Gillian M Borthwick
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, UK
    Ann Neurol 59:570-4. 2006
    ..We identified a patient with clinical features suggestive of MND but additional cardiac and metabolic symptoms. We wished to determine if the clinical features were due to a mitochondrial DNA mutation...
  78. ncbi request reprint Risk of developing a mitochondrial DNA deletion disorder
    Patrick F Chinnery
    Neurology, University of Newcastle upon Tyne, Newcastle upon Tyne, UK
    Lancet 364:592-6. 2004
    ..Many patients with mtDNA disease harbour a single pathogenic mtDNA deletion, but the risk factors for new cases and disease recurrence are not known...
  79. ncbi request reprint A novel point mutation in the mitochondrial tRNA(Trp) gene produces a neurogastrointestinal syndrome
    Katharina Maniura-Weber
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, UK
    Eur J Hum Genet 12:509-12. 2004
    ..The patient manifested a neurogastrointestinal syndrome with features including failure to thrive, psychomotor retardation, ophthalmoplegia, sensorineural deafness and encephalopathy together with vomiting, diarrhoea and colitis...
  80. pmc Mitochondrial DNA mutations in human colonic crypt stem cells
    Robert W Taylor
    Department of Neurology, The Medical School, University of Newcastle upon Tyne, United Kingdom
    J Clin Invest 112:1351-60. 2003
    ..These studies have important consequences not only for understanding of the finding of mtDNA mutations in aging tissues and tumors, but also for determining the frequency of mtDNA mutations within a cell...
  81. ncbi request reprint Childhood neurological presentation of a novel mitochondrial tRNA(Val) gene mutation
    Emma L Blakely
    Mitochondrial Research Group, School of Neurology, Neurobiology, and Psychiatry, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK
    J Neurol Sci 225:99-103. 2004
    ..This report further confirms the frequent association of mitochondrial tRNA mutation with neurological presentations, even in paediatric cases...
  82. ncbi request reprint A novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia
    Marcus Deschauer
    Department of Neurology, The Medical School, Framlington Place, University of Newcastle upon Tyne, NE2 4HH, Newcastle upon Tyne, UK
    Neuromuscul Disord 13:568-72. 2003
    ....
  83. doi request reprint Gastrointestinal tract involvement associated with the 3243A>G mitochondrial DNA mutation
    J Betts
    Mitochondrial Research Group, The Medical School, Framlington Place, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH, UK
    Neurology 70:1290-2. 2008
  84. ncbi request reprint Experimental strategies towards treating mitochondrial DNA disorders
    Julie L Gardner
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
    Biosci Rep 27:139-50. 2007
    ....
  85. pmc Detection and quantification of mitochondrial DNA deletions in individual cells by real-time PCR
    Langping He
    Department of Neurology, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK
    Nucleic Acids Res 30:e68. 2002
    ....
  86. doi request reprint Further pitfalls in the diagnosis of mtDNA mutations: homoplasmic mt-tRNA mutations
    H A L Tuppen
    Mitochondrial Research Group, Department of Neurology, Medical School, Newcastle University, Newcastle upon Tyne, UK
    J Med Genet 45:55-61. 2008
    ..These mutations must conform to specific pathogenic criteria, documenting unequivocally a functional defect of the mutant mt-tRNA...
  87. ncbi request reprint POLG1, C10ORF2, and ANT1 mutations are uncommon in sporadic progressive external ophthalmoplegia with multiple mitochondrial DNA deletions
    G Hudson
    Mitochondrial Research Group, The Medical School, University of Newcastle upon Tyne, UK
    Neurology 66:1439-41. 2006
    ..None had a mutation in C10ORF2 or ANT1. In the majority of patients, the primary nuclear genetic defect is likely to affect other unknown genes important for mtDNA maintenance...
  88. pmc Testing the adaptive selection of human mtDNA haplogroups: an experimental bioenergetics approach
    Joanna L Elson
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
    Biochem J 404:e3-5. 2007
    ....
  89. ncbi request reprint Multiple neonatal deaths due to a homoplasmic mitochondrial DNA mutation
    Robert McFarland
    Departments of Neurology, University of Newcastle upon Tyne, Newcastle upon Tyne, UK
    Nat Genet 30:145-6. 2002
    ..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...
  90. ncbi request reprint Nonrandom tissue distribution of mutant mtDNA
    P F Chinnery
    Department of Neurology, The University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
    Am J Med Genet 85:498-501. 1999
    ..The probability of observing any strict hierarchy in family is 4.82 x 10(-5). These results indicate that the distribution of the A3243G mutation is not solely determined by random processes...
  91. ncbi request reprint Homoplasmy, heteroplasmy, and mitochondrial dystonia
    R McFarland
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, University of Newcastle upon Tyne, Newcastle upon Tyne, UK
    Neurology 69:911-6. 2007
    ..A mitochondrial etiology was considered in each case because of the association of dystonia with other less prominent clinical features such as epilepsy...
  92. ncbi request reprint The epidemiology of pathogenic mitochondrial DNA mutations
    P F Chinnery
    Department of Neurology, The University of Newcastle upon Tyne, UK
    Ann Neurol 48:188-93. 2000
    ..These findings have resource implications, particularly for supportive care and genetic counseling...
  93. doi request reprint Reversible valproate hepatotoxicity due to mutations in mitochondrial DNA polymerase gamma (POLG1)
    R McFarland
    Newcastle upon Tyne NHS Hospitals Trust, Newcastle upon Tyne, UK
    Arch Dis Child 93:151-3. 2008
    ..Sequencing of the mitochondrial polymerase gamma gene (POLG1) revealed four heterozygous substitutions, two of which have been identified in cases of Alpers-Huttenlocher disease...
  94. ncbi request reprint Prevalence and progression of diabetes in mitochondrial disease
    R G Whittaker
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
    Diabetologia 50:2085-9. 2007
    ..3243A>G mutation...
  95. pmc The determination of complete human mitochondrial DNA sequences in single cells: implications for the study of somatic mitochondrial DNA point mutations
    R W Taylor
    Department of Neurology, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK
    Nucleic Acids Res 29:E74-4. 2001
    ..This technique will be particularly useful in identifying the mtDNA mutational spectra in age-related COX-negative cells and will increase our understanding of the pathogenetic mechanisms by which they occur...
  96. pmc Multi-system neurological disease is common in patients with OPA1 mutations
    P Yu-Wai-Man
    Mitochondrial Research Group, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
    Brain 133:771-86. 2010
    ....
  97. ncbi request reprint The epidemiology of mitochondrial disorders--past, present and future
    Andrew M Schaefer
    Mitochondrial Research Group, University of Newcastle upon Tyne, UK
    Biochim Biophys Acta 1659:115-20. 2004
    ....
  98. ncbi request reprint A neurological perspective on mitochondrial disease
    Robert McFarland
    Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
    Lancet Neurol 9:829-40. 2010
    ....
  99. pmc Mitochondrial DNA mutations in human disease
    Robert W Taylor
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, NE2 4HH, United Kingdom
    Nat Rev Genet 6:389-402. 2005
    ..However, many challenges remain, including the prevention and treatment of these diseases. This review explores the advances that have been made and the areas in which future progress is likely...
  100. ncbi request reprint High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease
    Andreas Bender
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH, UK
    Nat Genet 38:515-7. 2006
    ..Our studies suggest that somatic mtDNA deletions are important in the selective neuronal loss observed in brain aging and in Parkinson disease...
  101. ncbi request reprint Mitochondrial DNA transcription: regulating the power supply
    Robert W Taylor
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, Newcastle University, Newcastle upon Tyne, UK
    Cell 130:211-3. 2007
    ..This study highlights a mechanism by which mitochondrial DNA transcription (and therefore oxidative phosphorylation) may be regulated in response to alterations in the cell's physiological and metabolic demands...