leigh disease

Summary

Summary: A group of metabolic disorders primarily of infancy characterized by the subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, dysphagia, and lactic acidosis. Pathological features include spongy degeneration of the neuropile of the basal ganglia, thalamus, brain stem, and spinal cord. Patterns of inheritance include X-linked recessive, autosomal recessive, and mitochondrial. Leigh disease has been associated with mutations in genes for the PYRUVATE DEHYDROGENASE COMPLEX; CYTOCHROME-C OXIDASE; ATP synthase subunit 6; and subunits of mitochondrial complex I. (From Menkes, Textbook of Child Neurology, 5th ed, p850).

Top Publications

  1. ncbi The G13513A mutation in the ND5 gene of mitochondrial DNA as a common cause of MELAS or Leigh syndrome: evidence from 12 cases
    Sara Shanske
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Arch Neurol 65:368-72. 2008
  2. ncbi Pathogenic mitochondrial DNA mutations in protein-coding genes
    Lee Jun C Wong
    Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB2015, Houston, Texas 77030, USA
    Muscle Nerve 36:279-93. 2007
  3. ncbi Mutations in the gene encoding C8orf38 block complex I assembly by inhibiting production of the mitochondria-encoded subunit ND1
    Matthew McKenzie
    Centre for Reproduction and Development, Monash Institute of Medical Research, Clayton 3168, Australia
    J Mol Biol 414:413-26. 2011
  4. ncbi Diagnostic criteria for respiratory chain disorders in adults and children
    F P Bernier
    Murdoch Childrens Research Institute, Royal Children s Hospital, Flemington Road, Parkville VIC 3052, Australia
    Neurology 59:1406-11. 2002
  5. ncbi SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome
    Z Zhu
    Montreal Neurological Institute, Quebec, Canada
    Nat Genet 20:337-43. 1998
  6. pmc NDUFA10 mutations cause complex I deficiency in a patient with Leigh disease
    Saskia J G Hoefs
    Department of Paediatrics, Nijmegen Centre for Mitochondrial Disorders, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Eur J Hum Genet 19:270-4. 2011
  7. ncbi Clinical and molecular findings in children with complex I deficiency
    M Bugiani
    Department of Child Neurology, National Institute of Neurology C Besta, Milano, Italy
    Biochim Biophys Acta 1659:136-47. 2004
  8. ncbi Leigh and Leigh-like syndrome in children and adults
    Josef Finsterer
    Krankenanstalt Rudolfstiftung, Vienna, Austria
    Pediatr Neurol 39:223-35. 2008
  9. ncbi A novel mutation in the SURF1 gene in a child with Leigh disease, peripheral neuropathy, and cytochrome-c oxidase deficiency
    Claudio Bruno
    Neuromuscular Diseases Unit, Department of Pediatrics, University of Genova, Istituto Giannina Gaslini, Italy
    J Child Neurol 17:233-6. 2002
  10. ncbi Leigh disease presenting in utero due to a novel missense mutation in the mitochondrial DNA-ND3
    Esther Leshinsky-Silver
    Molecular Genetics Laboratory, Wolfson Medical Center, Holon, Israel
    Mol Genet Metab 100:65-70. 2010

Detail Information

Publications196 found, 100 shown here

  1. ncbi The G13513A mutation in the ND5 gene of mitochondrial DNA as a common cause of MELAS or Leigh syndrome: evidence from 12 cases
    Sara Shanske
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Arch Neurol 65:368-72. 2008
    ..Among these, mutations in the ND5 gene (OMIM 516005) of mitochondrial DNA are important, and the A13513A change has emerged as a hotspot...
  2. ncbi Pathogenic mitochondrial DNA mutations in protein-coding genes
    Lee Jun C Wong
    Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB2015, Houston, Texas 77030, USA
    Muscle Nerve 36:279-93. 2007
    ....
  3. ncbi Mutations in the gene encoding C8orf38 block complex I assembly by inhibiting production of the mitochondria-encoded subunit ND1
    Matthew McKenzie
    Centre for Reproduction and Development, Monash Institute of Medical Research, Clayton 3168, Australia
    J Mol Biol 414:413-26. 2011
    ..We conclude that C8orf38 is a crucial factor required for the translation and/or integration of ND1 into an early-stage assembly intermediate and that mutation of C8orf38 disrupts the initial stages of complex I biogenesis...
  4. ncbi Diagnostic criteria for respiratory chain disorders in adults and children
    F P Bernier
    Murdoch Childrens Research Institute, Royal Children s Hospital, Flemington Road, Parkville VIC 3052, Australia
    Neurology 59:1406-11. 2002
    ..Respiratory chain (RC) disorders are clinically, biochemically, and molecularly heterogeneous. The lack of standardized diagnostic criteria poses difficulties in evaluating diagnostic methodologies...
  5. ncbi SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome
    Z Zhu
    Montreal Neurological Institute, Quebec, Canada
    Nat Genet 20:337-43. 1998
    ..These data suggest a role for SURF1 in the biogenesis of the COX complex and define a new class of gene defects causing human neurodegenerative disease...
  6. pmc NDUFA10 mutations cause complex I deficiency in a patient with Leigh disease
    Saskia J G Hoefs
    Department of Paediatrics, Nijmegen Centre for Mitochondrial Disorders, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Eur J Hum Genet 19:270-4. 2011
    ..These results indicate that NDUFA10 is a novel candidate gene to screen for disease-causing mutations in patients with complex I deficiency...
  7. ncbi Clinical and molecular findings in children with complex I deficiency
    M Bugiani
    Department of Child Neurology, National Institute of Neurology C Besta, Milano, Italy
    Biochim Biophys Acta 1659:136-47. 2004
    ..The latter cases suggest the possibility of unconventional patterns of inheritance in complex I defects...
  8. ncbi Leigh and Leigh-like syndrome in children and adults
    Josef Finsterer
    Krankenanstalt Rudolfstiftung, Vienna, Austria
    Pediatr Neurol 39:223-35. 2008
    ..Associated mutations affect genes of the mitochondrial or nuclear genome. Leigh syndrome and Leigh-like syndrome are the mitochondrial disorders with the largest genetic heterogeneity...
  9. ncbi A novel mutation in the SURF1 gene in a child with Leigh disease, peripheral neuropathy, and cytochrome-c oxidase deficiency
    Claudio Bruno
    Neuromuscular Diseases Unit, Department of Pediatrics, University of Genova, Istituto Giannina Gaslini, Italy
    J Child Neurol 17:233-6. 2002
    ..showed a bilateral abnormal signal in the substantia nigra and in the subthalamic nucleus, suggestive of Leigh disease. Histochemical analysis of skeletal muscle showed decreased cytochrome-c oxidase activity...
  10. ncbi Leigh disease presenting in utero due to a novel missense mutation in the mitochondrial DNA-ND3
    Esther Leshinsky-Silver
    Molecular Genetics Laboratory, Wolfson Medical Center, Holon, Israel
    Mol Genet Metab 100:65-70. 2010
    ..We emphasize the importance of screening the mtDNA in pediatric patients as the first step in molecular diagnosis of Leigh syndrome...
  11. ncbi Peripheral neuropathy associated with mitochondrial disease in children
    Manoj P Menezes
    The Institute for Neuroscience and Muscle Research, The Children s Hospital at Westmead, Sydney, New South Wales, Australia
    Dev Med Child Neurol 54:407-14. 2012
    ..We therefore suggest that nerve conduction studies should be a part of the early evaluation of children with suspected mitochondrial disease...
  12. ncbi An adult case of Leigh disease
    Branko Malojcic
    Department of Neurology, University Hospital Centre Zagreb, Kispaticeva 12, 10 000 Zagreb, Croatia
    Clin Neurol Neurosurg 106:237-40. 2004
    ..results of muscle biopsy and the lack of response to corticosteroid treatment, led to the correct diagnosis of Leigh disease. Initiation of a ketogenic diet resulted in a rapid partial response...
  13. pmc The mitochondrial DNA G13513A MELAS mutation in the NADH dehydrogenase 5 gene is a frequent cause of Leigh-like syndrome with isolated complex I deficiency
    M Chol
    INSERM U393 and Department of Genetics, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France
    J Med Genet 40:188-91. 2003
    ....
  14. ncbi Leigh-like encephalopathy complicating Leber's hereditary optic neuropathy
    Benoit Funalot
    Service de Neurologie, Hopital Sainte Anne, Paris, France
    Ann Neurol 52:374-7. 2002
    ..This Leigh-like encephalopathy appears to be associated with a much more severe outcome than isolated Leber's hereditary optic neuropathy...
  15. pmc The role of the LRPPRC (leucine-rich pentatricopeptide repeat cassette) gene in cytochrome oxidase assembly: mutation causes lowered levels of COX (cytochrome c oxidase) I and COX III mRNA
    Fenghao Xu
    Metabolism Research Programme, The Research Institute, The Hospital for Sick Children, 555 University Ave, Toronto, ON, Canada M5G 1X8
    Biochem J 382:331-6. 2004
    ..A more diffuse distribution of LRPPRC in LSFC cells compared with controls was evident when viewed by immunofluorescence microscopy, with less LRPPRC present in peripheral mitochondria...
  16. pmc Defective complex I assembly due to C20orf7 mutations as a new cause of Leigh syndrome
    M Gerards
    Department of Genetics and Cell Biology, Unit Clinical Genomics, Maastricht University, Maastricht, The Netherlands
    J Med Genet 47:507-12. 2010
    ..The main cause is a deficiency in oxidative phosphorylation due to mutations in an mtDNA or nuclear oxidative phosphorylation gene...
  17. pmc Succinyl-CoA ligase deficiency: a mitochondrial hepatoencephalomyopathy
    Johan L K Van Hove
    Department of Pediatrics, University of Colorado Denver, Aurora, Colorado 80045, USA
    Pediatr Res 68:159-64. 2010
    ..a progressively severe myopathy with pronounced muscle weakness eventually leading to respiratory failure, Leigh disease, and recurrent hepatic failure...
  18. ncbi Clinical and laboratory survey of 65 Chinese patients with Leigh syndrome
    Yan Ling Yang
    Department of Pediatrics, Peking University First Hospital, Beijing 100034, China
    Chin Med J (Engl) 119:373-7. 2006
    ..In the current study, we performed a retrospective study in 65 patients in order to investigate the clinical and genetic characteristics of Leigh syndrome in Chinese patients...
  19. ncbi A SURF1 gene mutation presenting as isolated leukodystrophy
    S Rahman
    Department of Metabolic Medicine, Great Ormond Street Hospital, London, UK
    Ann Neurol 49:797-800. 2001
    ....
  20. ncbi Leigh-like subacute necrotising encephalopathy in Yorkshire Terriers: neuropathological characterisation, respiratory chain activities and mitochondrial DNA
    Kerstin Baiker
    Chair of General Pathology and Neuropathology, Institute of Veterinary Pathology, Ludwig Maximilians University of Munich, Munich, Germany
    Acta Neuropathol 118:697-709. 2009
    ..Mitochondrial tRNA mutations and large genetic rearrangements were excluded as underlying aetiology. Further studies, amongst relevant candidates, should focus on nuclear encoded transcription and translation factors...
  21. pmc Outpatient anesthesia for oral surgery in a juvenile with Leigh disease
    Zachary Ellis
    University of Texas Dental School, Health Science Center, San Antonio, Texas, USA
    Anesth Prog 52:70-3. 2005
    We report a case of anesthesia for elective outpatient third molar extraction in a juvenile with Leigh disease, a progressive neurodegenerative disorder related to respiratory chain deficiency...
  22. pmc Defects in energy homeostasis in Leigh syndrome French Canadian variant through PGC-1alpha/LRP130 complex
    Marcus P Cooper
    Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Genes Dev 20:2996-3009. 2006
    ..These data link LRP130 and PGC-1alpha to defective hepatic energy homeostasis in LSFC, and reveal a novel regulatory mechanism of glucose homeostasis...
  23. ncbi Leigh syndrome associated with mitochondrial complex I deficiency due to a novel mutation in the NDUFS1 gene
    Miguel A Martin
    Centro de Investigacion, Hospital Universitario 12 de Octubre, Madrid, Spain
    Arch Neurol 62:659-61. 2005
    ..Mutations in the nuclear-encoded subunits of complex I of the mitochondrial respiratory chain are a recognized cause of Leigh syndrome (LS). Recently, 6 mutations in the NDUFS1 gene were identified in 3 families...
  24. ncbi Expression and functional analysis of SURF1 in Leigh syndrome patients with cytochrome c oxidase deficiency
    J Yao
    Montreal Neurological Institute and Department of Human Genetics, McGill University, 3801 University Street, Montreal H3A 2B4, Canada
    Hum Mol Genet 8:2541-9. 1999
    ....
  25. ncbi Disorders related to mitochondrial membranes: pathology of the respiratory chain and neurodegeneration
    S Di Donato
    Division of Biochemistry and Genetics, Istituto Nazionale Neurologico C Besta, Milan, Italy
    J Inherit Metab Dis 23:247-63. 2000
    ..To better focus on OXPHOS genotype-phenotype correlations, mutations of the mtDNA-encoded structural genes are also discussed...
  26. ncbi Compound heterozygous mutations in the flavoprotein gene of the respiratory chain complex II in a patient with Leigh syndrome
    B Parfait
    INSERM U393, Hopital Necker Enfants Malades, Paris, France
    Hum Genet 106:236-43. 2000
    ..So far, profound deficiencies in complex II activity resulting from mutations in the Fp gene of the SDH present only as LS, a striking observation in view of the ubiquitous expression of this typical housekeeping gene in humans...
  27. ncbi Effect of various agents on adenosine triphosphate synthesis in mitochondrial complex I deficiency
    M Bar-Meir
    Metabolic Disease Unit, Shaare-Zedek Medical Center, Jerusalem, Israel
    J Pediatr 139:868-70. 2001
    ..The study of adenosine triphosphate production rate in fibroblasts may improve decision-making in treatment design of patients with respiratory chain defects...
  28. ncbi MRI in Leigh syndrome with SURF1 gene mutation
    Mario Savoiardo
    Ann Neurol 51:138-9. 2002
  29. pmc Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 genes in mitochondrial complex I deficiency
    P Benit
    INSERM U393, Service de Genetique, Hopital Necker Enfants Malades, 75015 Paris, France
    Am J Hum Genet 68:1344-52. 2001
    ..These results suggest that screening for complex I nuclear gene mutations is of particular interest in patients with complex I deficiency, even when normal respiratory-chain-enzyme activities in cultured fibroblasts are observed...
  30. ncbi Epidemiology of pediatric mitochondrial respiratory chain disorders in northwest Spain
    Manuel Castro-Gago
    Departamento de Pediatria, Servicio de Neuropediatría Hospital 12 de Octubre, Madrid, Spain
    Pediatr Neurol 34:204-11. 2006
    ..Sixteen of these patients manifested phenotypic syndromes that have not been previously reported in association with mitochondrial respiratory chain diseases...
  31. ncbi Leigh's syndrome
    A A S R Mannan
    Department of Pathology, All India Institute of Medical Sciences, New Delhi 110 029, India
    Indian J Pediatr 71:1029-33. 2004
    ....
  32. ncbi Cytochrome c oxidase partial deficiency-associated Leigh disease presenting as an extrapyramidal syndrome
    M Cacic
    Department of Pediatrics, Children s Hospital Zagreb, Croatia
    J Child Neurol 16:616-9. 2001
    b>Leigh disease is a subacute neurodegenerative disorder characterized by symmetric necrotic lesions in the basal ganglia, cerebellum, thalamus, brain stem, and optical nerves and caused by altered oxidative phosphorylation...
  33. pmc NDUFA2 complex I mutation leads to Leigh disease
    Saskia J G Hoefs
    Department of Pediatrics, Nijmegen Center for Mitochondrial Disorders, Radboud University Nijmegen Medical Center, Nijmegen 6500 HB, The Netherlands
    Am J Hum Genet 82:1306-15. 2008
    ..Furthermore, the mutation is associated with a mitochondrial depolarization. The expression and activity of complex I and the depolarization was (partially) rescued with a baculovirus system expressing the NDUFA2 gene...
  34. ncbi Leigh Syndrome with COX deficiency and SURF1 gene mutations: MR imaging findings
    Andrea Rossi
    Department of Pediatric Neuroradiology, G Gaslini Children s Research Hospital, Largo G Gaslini 5, I 16147 Genoa, Italy
    AJNR Am J Neuroradiol 24:1188-91. 2003
    ..MR imaging pattern recognition can suggest an underlying COX deficiency and should prompt investigators to search for SURF1 gene mutations...
  35. ncbi Genotyping microsatellite DNA markers at putative disease loci in inbred/multiplex families with respiratory chain complex I deficiency allows rapid identification of a novel nonsense mutation (IVS1nt -1) in the NDUFS4 gene in Leigh syndrome
    Paule Benit
    Département de génétique, Maternité and INSERM U393, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015, Paris, France
    Hum Genet 112:563-6. 2003
    ..More generally, we suggest giving consideration to a more systematic microsatellite analysis of putative disease loci for identification of disease genes in inbred/multiplex families affected with genetically heterogeneous conditions...
  36. ncbi [A new missense mutation of 574C>T in the SURF1 gene--biochemical and molecular genetic study in seven children with Leigh syndrome]
    M Capková
    Klinika dĕtského a dorostového lékarství a Centrum integrované genomiky 1 LF UK a VFN, Praha
    Cas Lek Cesk 141:636-41. 2002
    b>Leigh disease, subacute necrotizing encephalopathy, is a serious mitochondrial disorder of energy-providing metabolism...
  37. ncbi SURF1 gene mutations in three cases with Leigh syndrome and cytochrome c oxidase deficiency
    A R Moslemi
    Department of Pathology, Sahlgrenska University Hospital, Goteborg, Sweden
    Neurology 61:991-3. 2003
    ..The authors have identified four pathogenic mutations including a novel, in-frame, 15-bp tandem duplication (806-820) in exon 8 and a novel 751+1G>A splice site mutation in SURF1 in three cases of LS with COX deficiency...
  38. ncbi A novel recurrent mitochondrial DNA mutation in ND3 gene is associated with isolated complex I deficiency causing Leigh syndrome and dystonia
    Emmanuelle Sarzi
    INSERM U781, Department of Genetics, Hopital Necker Enfants Malades, Paris, France
    Am J Med Genet A 143:33-41. 2007
    ..These results show that the 10197G>A mutation in the mitochondrial ND3 gene should be considered as a common mtDNA mutation responsible for LS and dystonia...
  39. ncbi 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...
  40. pmc Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome
    P Benit
    Unité de Recherche sur les Handicaps Génétiques de l Enfant INSERM U393 and Département de Génétique, Hopital Necker Enfants Malades, Paris Cedex 15, France
    J Med Genet 41:14-7. 2004
    ..The reasons for these differences are uncertain...
  41. ncbi Maternal segmental disomy in Leigh syndrome with cytochrome c oxidase deficiency caused by homozygous SURF1 mutation
    A K J van Riesen
    Department of Pediatrics and Pediatric Neurology, Georg August University Goettingen, Robert Koch Strasse 40, 37075 Goettingen, Germany
    Neuropediatrics 37:88-94. 2006
    ..This case of segmental isodisomy illustrates that genotyping of parents is crucial for correct genetic counseling...
  42. pmc Late-onset Leigh syndrome in a patient with mitochondrial complex I NDUFS8 mutations
    Vincent Procaccio
    Center for Molecular and Mitochondrial Medicine and Genetics MAMMAG, University of California, Irvine 92697 3940, USA
    Neurology 62:1899-901. 2004
    ..Western blot analysis revealed a deficiency in the NDUFS8 polypeptide, but also reductions in other nuclear subunits of complex I, suggesting that this subunit is essential for either the assembly or stability of complex I...
  43. pmc Functional and genetic studies demonstrate that mutation in the COX15 gene can cause Leigh syndrome
    C E Oquendo
    J Med Genet 41:540-4. 2004
  44. ncbi Novel SURF1 mutation in a child with subacute encephalopathy and without the radiological features of Leigh Syndrome
    Leonardo Salviati
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York, USA
    Am J Med Genet A 128:195-8. 2004
    ..These data confirm that the spectrum of MRI findings in LS is variable and that SURF1 mutations should be considered in patients with encephalomyopathy and COX deficiency even when early MRI findings are negative...
  45. pmc Recurrent de novo mitochondrial DNA mutations in respiratory chain deficiency
    S Lebon
    INSERM U393, Department of Genetics, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France
    J Med Genet 40:896-9. 2003
    ..The recurrent mutations consistently involved T-->C transitions (p<10(-4)). This study supports the view that an efficient molecular screening should be based on an accurate identification of respiratory chain enzyme deficiency...
  46. ncbi Leigh syndrome associated with a mutation in the NDUFS7 (PSST) nuclear encoded subunit of complex I
    R H Triepels
    Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, University Children s Hospital, The Netherlands
    Ann Neurol 45:787-90. 1999
    ..We report the first missense mutation within the nuclear encoded complex I subunit, NDUFS7, in 2 siblings with neuropathologically proven complex I-deficient Leigh syndrome...
  47. pmc The first nuclear-encoded complex I mutation in a patient with Leigh syndrome
    J Loeffen
    Department of Pediatrics, Nijmegen Center for Mitochondrial Disorders, The Netherlands
    Am J Hum Genet 63:1598-608. 1998
    ..In the 19 other patients with enzymatic complex I deficiency, no mutations were found in the NDUFS8 cDNA. This article describes the first molecular genetic link between a nuclear-encoded subunit of complex I and Leigh syndrome...
  48. ncbi Mitochondrial complex I deficiency caused by a deleterious NDUFA11 mutation
    Itai Berger
    Pediatric Neurology Unit, Hadassah Hebrew University Medical Center, Jerusalem
    Ann Neurol 63:405-8. 2008
    ..Mutation analysis of the NDUFA11 is warranted in isolated complex I deficiency presenting with infantile lactic acidemia or encephalocardiomyopathy...
  49. pmc A genomewide linkage-disequilibrium scan localizes the Saguenay-Lac-Saint-Jean cytochrome oxidase deficiency to 2p16
    N Lee
    Metabolism Research Programme, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
    Am J Hum Genet 68:397-409. 2001
    ..Although the LSFC gene remains to be elucidated, the present study demonstrates the feasibility of using a genomewide LD strategy to localize the critical region for a rare genetic disease in a founder population...
  50. ncbi 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...
  51. ncbi Molecular genetic characterization of an X-linked form of Leigh's syndrome
    P M Matthews
    Department of Biochemistry, University of Oxford, UK
    Ann Neurol 33:652-5. 1993
    ..As the E1 alpha subunit is encoded on the X chromosome, this observation confirms that some patients with Leigh's syndrome may potentially exhibit X-linked inheritance...
  52. ncbi Leigh disease associated with a novel mitochondrial DNA ND5 mutation
    Robert W Taylor
    Department of Neurology, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK
    Eur J Hum Genet 10:141-4. 2002
    b>Leigh disease is a genetically heterogeneous, neurodegenerative disorder of childhood that is caused by defects of either the nuclear or mitochondrial genome...
  53. pmc Light and electron microscopy characteristics of the muscle of patients with SURF1 gene mutations associated with Leigh disease
    M Pronicki
    Department of Pathology, The Children s Memorial Health Institute, Warsaw, Poland
    J Clin Pathol 61:460-6. 2008
    ..The aim of the present work is to assess the skeletal muscle morphology coexisting with SURF1 mutations from our own research and in the literature...
  54. ncbi Facial dysmorphism in Leigh syndrome with SURF-1 mutation and COX deficiency
    Adnan Yuksel
    Department of Medical Genetic, Division of Pediatric Neurology, Cerrahpasa Medical Faculty, Istanbul University, Turkey
    Pediatr Neurol 34:486-9. 2006
    ..SURF-1 gene mutations must be particularly reviewed in such patients...
  55. ncbi Decreased affinity for oxygen of cytochrome-c oxidase in Leigh syndrome caused by SURF1 mutations
    Petr Pecina
    Institute of Physiology and Center for Integrated Genomics, Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic
    Am J Physiol Cell Physiol 287:C1384-8. 2004
    ..These results suggest that at physiologically low intracellular PO2, the depressed oxygen affinity may lead in vivo to limitations of respiration, resulting in impaired energy provision in Leigh syndrome patients...
  56. ncbi Missense mutations in SURF1 associated with deficient cytochrome c oxidase assembly in Leigh syndrome patients
    A Poyau
    Centre de Genetique Moleculaire et Cellulaire, UMR 5534, Centre National de la Recherche Scientifique, Université Claude Bernard de Lyon I, Villeurbanne, France
    Hum Genet 106:194-205. 2000
    ..COX activity could be restored in fibroblasts of the three patients by complementation with a retroviral vector containing normal SURF1 cDNA. These mutations identify domains essential to Surf1 protein structure and/or function...
  57. pmc Mitochondrial DNA background modifies the bioenergetics of NARP/MILS ATP6 mutant cells
    M D'Aurelio
    Weill Medical College of Cornell University, New York, NY 10065, USA
    Hum Mol Genet 19:374-86. 2010
    ..Taken together, these results indicate that the mtDNA background plays an important role in modulating the biochemical defects and clinical outcome in NARP/MILS...
  58. ncbi Diagnostic difficulties with common SURF1 mutations in patients with cytochrome oxidase-deficient Leigh syndrome
    R A Head
    Genetics Unit, Department of Biochemistry, University of Oxford, UK
    J Inherit Metab Dis 27:57-65. 2004
    ..These patients emphasize the need to perform mutation analysis on both cDNA and genomic DNA wherever possible...
  59. ncbi A novel mutation in SURF1 causes skipping of exon 8 in a patient with cytochrome c oxidase-deficient leigh syndrome and hypertrichosis
    S L Williams
    University Department of Clinical Neurosciences, Royal Free and University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, United Kingdom
    Mol Genet Metab 73:340-3. 2001
    ..cDNA sequencing demonstrated that this deletion results in a messenger lacking exon 8. RT-PCR experiments suggested a rapid degradation of the aberrant mRNA species from the 5'-end...
  60. ncbi Abnormal calcium homeostasis in fibroblasts from patients with Leigh disease
    M Wasniewska
    Department of Cellular Biochemistry, Nencki Institute of Experimental Biology, 3 Pasteur Street, Warsaw, 02 093, Poland
    Biochem Biophys Res Commun 283:687-93. 2001
    ..In the present work, we examined the activation of SOCs in fibroblasts derived from three patients with Leigh disease (LS). We identified mutations in the SURF-1 gene in all these cells...
  61. ncbi Three novel SURF-1 mutations in Japanese patients with Leigh syndrome
    Yukiko Ogawa
    Department of Pediatrics, School of Medicine, University of Tokushima, Tokushima, Japan
    Pediatr Neurol 26:196-200. 2002
    ....
  62. ncbi Two novel mutations of SURF1 in Leigh syndrome with cytochrome c oxidase deficiency
    M Teraoka
    Department of Pediatrics, Okayama University Medical School, Japan
    Hum Genet 105:560-3. 1999
    ..Therefore, we concluded that the patient was a compound heterozygote with these mutations. These are the first pathogenetic SURF1 mutations identified in a Japanese family...
  63. ncbi Leigh disease: clinical, neuroradiologic, and biochemical study of three new cases with cytochrome c oxidase deficiency
    S Savasta
    Division of Pediatrics and Neonatology, Istituti Ospitaleri, Cremona, Italy
    J Child Neurol 16:608-13. 2001
    Three cases of Leigh disease are described. In all three, symptoms began in the first months of life, with muscle hypotonia, lactic acidosis, and psychomotor delay...
  64. ncbi Unusual clinical presentations in four cases of Leigh disease, cytochrome C oxidase deficiency, and SURF1 gene mutations
    Stacey K H Tay
    Department of Neurology, Columbia University, New York, NY, USA
    J Child Neurol 20:670-4. 2005
    Mutations in the SURF1 gene are the most frequent causes of Leigh disease with cytochrome c oxidase deficiency...
  65. pmc Clinical and molecular features of an infant patient affected by Leigh Disease associated to m.14459G>A mitochondrial DNA mutation: a case report
    Dario Ronchi
    Centro Dino Ferrari, Department of Neurological Sciences, University of Milan, Foundation IRCCS Ca Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
    BMC Neurol 11:85. 2011
    ..Onset is in early infancy and prognosis is poor. Causative mutations have been disclosed in mitochondrial DNA and nuclear genes affecting respiratory chain subunits and assembly factors...
  66. ncbi Hypertrichosis in patients with SURF1 mutations
    Elsebet Ostergaard
    John F Kennedy Institute, Glostrup, Denmark
    Am J Med Genet A 138:384-8. 2005
    ....
  67. ncbi A Chinese girl with Leigh syndrome: effect of botulinum toxin on dystonia
    T F Leung
    Department of Paediatrics, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong
    J Paediatr Child Health 34:480-2. 1998
    ..Dystonia persisted despite treatments with muscle relaxants and a ketogenic diet. Intramuscular botulinum toxin resulted in significant relief of dystonia...
  68. ncbi Leigh syndrome due to compound heterozygosity of dihydrolipoamide dehydrogenase gene mutations. Description of the first E3 splice site mutation
    Olga Grafakou
    Nijmegen Centrer for Mitochondrial Disorders, University Medical Centre Nijmegen, Department of Paediatrics, Geert Grooteplein 10, 9101, 6500HB Nijmegen, The Netherlands
    Eur J Pediatr 162:714-8. 2003
    ..A heterozygous polymorphism was also detected. In the patient's cDNA the I393T mutation and the polymorphism appeared to be homozygous, indicating that the mRNA coming from the IVS9+1G>A mutant allele is not stable...
  69. ncbi A novel mutation of the NDUFS7 gene leads to activation of a cryptic exon and impaired assembly of mitochondrial complex I in a patient with Leigh syndrome
    Sophie Lebon
    Service de Génétique and INSERM U781, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France
    Mol Genet Metab 92:104-8. 2007
    ..These results report the first intronic NDUFS7 gene mutation and demonstrate the crucial role of NDUFS7 in the biogenesis of complex I...
  70. ncbi New splicing-site mutations in the SURF1 gene in Leigh syndrome patients
    M O Pequignot
    Laboratoire CERTO, , 156 rue de Vaugirard, 75015 Paris, France
    J Biol Chem 276:15326-9. 2001
    ..We also show that Surf1 protein is not implicated in the assembly of other respiratory chain complexes or the pyruvate dehydrogenase complex...
  71. ncbi A novel mutation in the human complex I NDUFS7 subunit associated with Leigh syndrome
    Sophie Lebon
    INSERM U781, Hopital Necker Enfants Malades, Paris, France
    Mol Genet Metab 90:379-82. 2007
    ..Identifying nuclear mutations as a cause of respiratory chain disorders will enhance the possibility of prenatal diagnosis and help us to understand how moleculardefects can lead to complex I deficiency...
  72. ncbi Impaired complex I assembly in a Leigh syndrome patient with a novel missense mutation in the ND6 gene
    Cristina Ugalde
    Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands
    Ann Neurol 54:665-9. 2003
    ....
  73. ncbi Cardiomyopathy associated with neurologic disorders and mitochondrial phenotype
    Jose Marin-Garcia
    Molecular Cardiology and Neuromuscular Institute, Highland Park, NJ 08904, USA
    J Child Neurol 17:759-65. 2002
    ..cardiomyopathy and neurologic disorders including seizures, dystonia, ophthalmoplegia, Kearns-Sayre syndrome, Leigh disease, and Friedreich's ataxia. All tissues examined displayed marked defects in respiratory complex activities...
  74. ncbi Humanin expression in skeletal muscles of patients with chronic progressive external ophthalmoplegia
    Tesseki Kin
    Department of Neurology, Nara Medical University School of Medicine, 840 Shijo Cho, Kashihara, Nara 634 8522, Japan
    J Hum Genet 51:555-8. 2006
    ..Collectively, our findings suggest that HN may be specifically expressed in response to defects in energy production in muscles with mitochondrial abnormalities...
  75. ncbi Two new mutations in the MTATP6 gene associated with Leigh syndrome
    A R Moslemi
    Department of Pathology, Sahlgrenska University Hospital, Goteborg, Sweden
    Neuropediatrics 36:314-8. 2005
    ..This mutation was absent in the patient's parents and sister suggesting that the mutation was de novo. Our findings expand the spectrum of mutations causing LS and emphasize the role of MTATP6 gene mutations in pathogenesis of LS...
  76. ncbi Bull's-eye maculopathy in an infant with Leigh disease
    Philip W Laird
    Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Am J Ophthalmol 142:186-7. 2006
    To report a bull's-eye maculopathy-like fundus abnormality in an infant with Leigh disease.
  77. ncbi Biochemical phenotypes associated with the mitochondrial ATP6 gene mutations at nt8993
    Alessandra Baracca
    Dipartimento di Biochimica G Moruzzi, Via Irnerio 48, Universita di Bologna, 40126 Bologna, and Fondazione Ospedale Maggiore IRCCS Centro Dino Ferrari, Milano, Italy
    Biochim Biophys Acta 1767:913-9. 2007
    ....
  78. ncbi Allotopic mRNA localization to the mitochondrial surface rescues respiratory chain defects in fibroblasts harboring mitochondrial DNA mutations affecting complex I or v subunits
    Crystel Bonnet
    Laboratoire de Physiopathologie Cellulaire et Moleculaire de la Retine, INSERM U592, Université Pierre et Marie Curie UPMC Paris6, Hôpital St Antoine Bât Kourilsky, 184 rue du Faubourg Saint Antoine, 75571 Paris Cedex 12, France
    Rejuvenation Res 10:127-44. 2007
    ..Therefore, mRNA sorting to the mitochondrial surface represents a powerful strategy that could ultimately be applied in human therapy and become available for an array of devastating disorders caused by mtDNA mutations...
  79. ncbi G8363A mitochondrial DNA mutation is not a rare cause of Leigh syndrome - clinical, biochemical and pathological study of an affected child
    Maciej Pronicki
    Department of Pathology, The Children s Memorial Health Institute, Aleja Dzieci Polskich 20, 04 730 Warsaw, Poland
    Folia Neuropathol 45:187-91. 2007
    ..Postmortem examination confirmed the presence of typical LS central nervous system lesions as well as hypertrophy of the left ventricle of the heart...
  80. ncbi The neurological evolution of Pearson syndrome: case report and literature review
    Hsiu Fen Lee
    Department of Pediatrics, Taichung Veterans General Hospital, No 160, Sec 3 Taichung Kang Road, Taichung 407, Taiwan, ROC
    Eur J Paediatr Neurol 11:208-14. 2007
    ..Pearson syndrome (PS) is an uncommon specific syndrome among mitochondrial diseases. It has unique clinical presentations...
  81. pmc Mutations in the ND5 subunit of complex I of the mitochondrial DNA are a frequent cause of oxidative phosphorylation disease
    M J Blok
    Department of Clinical Genetics, University Hospital, Maastricht, The Netherlands
    J Med Genet 44:e74. 2007
    ..However, mutations in other mtDNA regions can be an important cause of oxidative phosphorylation (OXPHOS) disease as well...
  82. ncbi Clinical and molecular survey in 124 Chinese patients with Leigh or Leigh-like syndrome
    Y Zhang
    Department of Pediatrics, Peking University First Hospital, Beijing, PR China
    J Inherit Metab Dis 30:265. 2007
    ..Only one patient had C214T mutation in the pyruvate dehydrogenase E1alpha subunit gene. In the remaining 92 patients (74.2%), a specific molecular dysfunction or underlying metabolic abnormality could not be identified...
  83. ncbi SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness
    Rosalba Carrozzo
    Unit of Molecular Medicine, Bambino Gesu Children s Hospital, Rome, Italy
    Brain 130:862-74. 2007
    ..We confirm and extend the findings on this inborn error of metabolism in the TCA cycle that must be carefully investigated by accurate metabolite analyses...
  84. ncbi The mitochondrial 13513G>A mutation is associated with Leigh disease phenotypes independent of complex I deficiency in muscle
    Ariel Brautbar
    Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB 2015, Houston, TX 77030, USA
    Mol Genet Metab 94:485-90. 2008
    ..Recent observations have linked this mutation to Leigh disease. We screened for the 13513G>A mutation in a cohort of 265 patients with Leigh and Leigh-like disease...
  85. ncbi A previously undescribed leukodystrophy in Leigh syndrome associated with T9176C mutation of the mitochondrial ATPase 6 gene
    Po Cheng Hung
    Division of Pediatric Neurology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan
    Dev Med Child Neurol 49:65-7. 2007
    ..However, leukodystrophy in Leigh syndrome associated with m.9176T>C mutation has never been reported before. We suggest that m.9176T>C mutation could be a new aetiology for leukodystrophy in children with Leigh syndrome...
  86. ncbi The mitochondrial 13513G > A mutation is most frequent in Leigh syndrome combined with reduced complex I activity, optic atrophy and/or Wolff-Parkinson-White
    E Mariken Ruiter
    Radboud University Nijmegen Medical Centre, Department of Human Genetics, Nijmegen, The Netherlands
    Eur J Hum Genet 15:155-61. 2007
    ..In addition, we confirmed that the adjacent m.13514A > G mutation is a rare cause of LS or MELAS since no cases with this transition were found...
  87. ncbi [The molecular background of Leigh syndrome]
    Dorota Piekutowska-Abramczuk
    Instytut Pomnik Centrum Zdrowia Dziecka, Zakład Genetyki Medycznej, Al Dzieci Polskich 20, 04 730 Warszawa
    Neurol Neurochir Pol 42:238-50. 2008
    ..Leigh syndrome occurs with an estimated frequency of 1:77,000-1:34,000 live births. The disease demonstrates maternal, X-linked, and autosomal recessive inheritance...
  88. ncbi Infantile mitochondrial disorders
    Rosalba Carrozzo
    Molecular Medicine, IRCCS Bambino Gesù Hospital, Piazza S Onofrio 4, 00165, Rome, Italy
    Biosci Rep 27:105-12. 2007
    ..We will report some of the major clinical phenotypes observed in infancy, their underlining molecular features, and will propose an approach to reach a more complete diagnosis...
  89. ncbi Novel mitochondrial mutation in the ND4 gene associated with Leigh syndrome
    A Vanniarajan
    Centre for Cellular and Molecular Biology, Hyderabad, India
    Acta Neurol Scand 114:350-3. 2006
    ..As the mutation observed in this study was novel and homoplasmic, we speculate that there could be interplay of this mitochondrial mutation along with nuclear gene(s) in the pathogenesis...
  90. pmc Analysis of mitochondrial DNA sequences in childhood encephalomyopathies reveals new disease-associated variants
    Aijaz A Wani
    National Centre for Cell Science, Pune, India
    PLoS ONE 2:e942. 2007
    ..We analyzed the mtDNA sequences from a group of 23 pediatric patients with clinical and morphological features of mitochondrial encephalopathies and tried to establish a relationship of identified variants with the disease...
  91. ncbi A new mitochondrial DNA mutation in ND3 gene causing severe Leigh syndrome with early lethality
    Marco Crimi
    Centro Dino Ferrari, Department of Neurological Sciences, University of Milan, IRCCS Ospedale Maggiore Policlinico, Centro di Eccellenza per le malattie Neuro Degenerative, 20122 Milano, Italy
    Pediatr Res 55:842-6. 2004
    ..The transition changes a serine residue into a proline, in a highly conserved region of the NADH dehydrogenase subunit 3 (ND3). This is the first description of a mitochondrial ND3 gene in Leigh syndrome with early lethality...
  92. ncbi [Defects of pyruvate metabolism in cultured lymphoblastoid cells of 20 patients with Leigh syndrome]
    E Naito
    Department of Pediatrics, School of Medicine, University of Tokushima
    No To Hattatsu 28:495-500. 1996
    ..These results indicate that the underlying defects in Leigh syndrome are heterogeneous and cultured lymphoblastoid cells are very useful materials for diagnosis of the etiology of Leigh syndrome...
  93. ncbi Familial mtDNA T8993C transition causing both the NARP and the MILS phenotype in the same generation. A morphological, genetic and spectroscopic study
    Monica Sciacco
    J Neurol 250:1498-500. 2003
  94. ncbi [Cytochrome c oxidase deficiency--SURF1 mutations]
    Etsuo Naito
    Department of Pediatrics, School of Medicine, University of Tokushima
    Nihon Rinsho 60:446-9. 2002
  95. ncbi Infantile spasms with basal ganglia MRI hypersignal may reveal mitochondrial disorder due to T8993G MT DNA mutation
    I Desguerre
    Service de Neuropediatrie, Hopital Saint Vincent de Paul, 74 Avenue Denfert Rochereau, 75014 Paris, France
    Neuropediatrics 34:265-9. 2003
    ..To report three cases of infantile spasms (IS) with an abnormal magnetic resonance imaging signal in the basal ganglia (Leigh-like syndrome), due to T8993G mt DNA mutation...
  96. ncbi Atypical Leigh syndrome associated with the D393N mutation in the mitochondrial ND5 subunit
    V Petruzzella
    Department of Medical Biochemistry and Medical Biology, University of Bari, Italy
    Neurology 61:1017-8. 2003
  97. ncbi Mutation screening in patients with isolated cytochrome c oxidase deficiency
    Sabrina Sacconi
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Pediatr Res 53:224-30. 2003
    ..These data show that heterogeneous clinical phenotypes are associated with COX deficiency, that mutations in mtDNA COX genes are rare, and that mutations in additional genes remain to be identified...
  98. ncbi Low mutant load of mitochondrial DNA G13513A mutation can cause Leigh's disease
    Denise M Kirby
    Murdoch Children s Research Institute, University of Melbourne, Victoria, Australia
    Ann Neurol 54:473-8. 2003
    ..We conclude that the G13513A mutation causes a complex I defect when present at unusually low mutant load and may act dominantly...
  99. ncbi [Complex IV(cytochrome c oxidase)]
    Kazuma Sugie
    Department of Ultrastructural Research and Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry
    Nihon Rinsho 60:490-4. 2002
  100. ncbi [Mitochondrial DNA T to G mutation 8993 in Leigh encephalopathy and organic aciduria]
    M Ueno
    Division of Child Neurology, Institute of Neurological Sciences, Tottori University, Faculty of Medicine, Yonago, Tottori
    No To Hattatsu 33:276-9. 2001
    ..In this case, mitochondrial DNA mutation may have caused organic aciduria and the atypical imaging findings...
  101. ncbi Leigh disease with mitochondrial DNA A8344G mutation: case report and brief review
    Chang Yong Tsao
    Department of Pediatrics, The Ohio State University, Children s Radiological Institute, Children s Hospital, Columbus, USA
    J Child Neurol 18:62-4. 2003
    b>Leigh disease, subacute necrotizing encephalomyelopathy, is a neurodegenerative disorder often seen in infancy or childhood but rarely reported in adults...

Research Grants23

  1. Complex I: Role of L Subunit in Proton Translocation
    Steven B Vik; Fiscal Year: 2011
    ..alleles are known to be causative for fatal disorders such as Leber's hereditary optic neuropathy (LHON), Leigh disease, and mitochondrial encephalomyopathy and lactic acidosis with stroke-like episodes (MELAS)...
  2. Biosynthetic Protein Models of Heme-copper Oxidases and Nitric Oxide Reductases
    Yi Lu; Fiscal Year: 2013
    ..Therefore the work will make important contributions to healthcare, as it will provide a molecular basis for understanding two enzymes important to human health. ..
  3. Nuclear Control of Mitochondrial Gene Expression
    Gerald Shadel; Fiscal Year: 2013
    ..Knowledge gained from these studies holds therapeutic promise for mitochondrial disease and age-related pathology based on augmenting mitochondrial gene expression and directly addresses the human disorders obesity and Leigh Syndrome. ..
  4. Molecular Pathogenesis of Coenzyme Q10 Deficiency
    Michio Hirano; Fiscal Year: 2012
    ..Aim 4: In collaboration with Professor Pl[unreadable]cido Navas, University of Sevilla, Spain, we will characterize CoQ10 biosynthetic genes and mutations in yeast. ..
  5. ELECTROPHYSIOLOGY OF NEONATAL AND ADULT HEART
    Martin Morad; Fiscal Year: 2013
    ....
  6. Detection of S-(2-succino)cysteine (2SC) as a Biomarker of Mitochondrial Disease
    Norma Frizzell; Fiscal Year: 2013
    ..We will also explore a therapeutic intervention which should lower NADH levels, reduce fumarate and thereby prevent increased protein succination, opening novel therapeutic avenues for the future treatment of mitochondrial diseases. ..
  7. Fo Motor Mechanisms that Power FoF1 ATP Synthesis
    Wayne D Frasch; Fiscal Year: 2013
    ..Some patients with cardiomyopathies or Parkinson's disease also have increased damage to these genes. All independent life forms use the FoF1 as the main source of cellular ATP. ..
  8. Pyruvate Dehydrogenase E1: Structure-Function Studies
    William F Furey; Fiscal Year: 2012
    ....
  9. Assembly of Redox Metal Centers in Cytochrome Oxidase
    Dennis R Winge; Fiscal Year: 2013
    ..The most frequently mutated gene in Leigh Syndrome patients is SURF1 that encodes a protein that acts in heme a insertion in cytochrome oxidase. ..
  10. How does mitochondrial dysfunction cause neurodegeneration?
    THOMAS ROBERT CLANDININ; Fiscal Year: 2012
    ..Importantly, however, rare genetic conditions such as Leigh Disease directly affect mitochondrial function and cause neurodegeneration in infants and children...
  11. Mitochondrial Transcription and Pediatric Disease
    NEAL J SONDHEIMER; Fiscal Year: 2013
    ..The proposal overall advances the goal of studying biochemical processes and metabolism as these relate to brain functioning, injury and long term consequences to the brain. ..
  12. FACSVantage SE Upgrade
    RAYMOND HESTER; Fiscal Year: 2004
    ....
  13. Mouse Modeling of Leigh Disease and Complex I Assembly
    Carl Pinkert; Fiscal Year: 2007
    ..genes are intimately associated with various metabolic diseases including severe childhood disorders including Leigh disease. Leigh disease is a neurodegenerative mitochondrial disorder characterized by a motor control loss and ..
  14. Transcriptional profiling in childhood diseases
    William Craigen; Fiscal Year: 2006
    ..These results will help in counseling, the development of potential therapies, and assessing long-term outcomes. ..
  15. A Genetic Model of Leigh Syndrome Suppression in Drosophila
    Satpal Singh; Fiscal Year: 2009
    ..The proposed studies would provide leads on the mechanisms underlying these disorders and on possible therapeutic approaches to treat them. ..
  16. ATP SYNTHESIS IN MITOCHONDRIAL DISORDERS
    Giovanni Manfredi; Fiscal Year: 2003
    ..Allotopic expression of the recoded wild-type genes should partially restore the APT synthetic function in mutant cells. ..
  17. CLINICAL RESEARCH CENTER FOR NEUROMUSCULAR DISEASE
    Salvatore DiMauro; Fiscal Year: 2007
    ....
  18. The Role of Mitochondrial DNA Alterations in Cancer
    Lee Jun Wong; Fiscal Year: 2008
    ..Results from this research project will help us understand the functional role of mitochondrial DNA alterations in cancer and identify potential novel targets for more effective therapeutic development. ..
  19. Epigenetic Regulation of Mitochondiral Complex II
    Gerald S Shadel; Fiscal Year: 2010
    ..Understanding the molecular basis of imprinting in PGL may provide general insights on how differential expression of a single defective gene can lead to disease or normalcy. ..
  20. scVEGF Targeted Radiotherapy of Mammary and Colonic Cancer
    FRANCIS GERARD BLANKENBERG; Fiscal Year: 2010
    ..Successful completion of our proposal will give the needed preclinical data for pursuing scVEGF targeted radiotherapy in other models and ultimately clinical applications. ..
  21. Transmission genetics of mammalian mitochondrial DNA
    Eric Shoubridge; Fiscal Year: 2008
    ..abstract_text> ..
  22. IMAGING APOPTOSIS IN VIVO WITH TECHNETIUM 99M ANNEXIN
    Francis Blankenberg; Fiscal Year: 2007
    ..Completion of this proposal will aid in the design and planning of clinical trials that will study the use of serial annexin V imaging as a non-invasive marker of cellular injury and therapeutic efficacy. ..
  23. IMAGING APOPTOSIS IN VIVO WITH TECHNETIUM 99M ANNEXIN
    Francis Blankenberg; Fiscal Year: 2001
    ..abstract_text> ..