Genomes and Genes
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).
Publications196 found, 100 shown here
- The G13513A mutation in the ND5 gene of mitochondrial DNA as a common cause of MELAS or Leigh syndrome: evidence from 12 casesSara 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...
- Pathogenic mitochondrial DNA mutations in protein-coding genesLee 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....
- Mutations in the gene encoding C8orf38 block complex I assembly by inhibiting production of the mitochondria-encoded subunit ND1Matthew 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...
- Diagnostic criteria for respiratory chain disorders in adults and childrenF 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...
- SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndromeZ 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...
- NDUFA10 mutations cause complex I deficiency in a patient with Leigh diseaseSaskia 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...
- Clinical and molecular findings in children with complex I deficiencyM 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...
- Leigh and Leigh-like syndrome in children and adultsJosef 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...
- A novel mutation in the SURF1 gene in a child with Leigh disease, peripheral neuropathy, and cytochrome-c oxidase deficiencyClaudio 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...
- Leigh disease presenting in utero due to a novel missense mutation in the mitochondrial DNA-ND3Esther 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...
- Peripheral neuropathy associated with mitochondrial disease in childrenManoj 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...
- An adult case of Leigh diseaseBranko 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...
- The mitochondrial DNA G13513A MELAS mutation in the NADH dehydrogenase 5 gene is a frequent cause of Leigh-like syndrome with isolated complex I deficiencyM 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....
- Leigh-like encephalopathy complicating Leber's hereditary optic neuropathyBenoit 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...
- 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 mRNAFenghao 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...
- Defective complex I assembly due to C20orf7 mutations as a new cause of Leigh syndromeM 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...
- Succinyl-CoA ligase deficiency: a mitochondrial hepatoencephalomyopathyJohan 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...
- Clinical and laboratory survey of 65 Chinese patients with Leigh syndromeYan 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...
- A SURF1 gene mutation presenting as isolated leukodystrophyS Rahman
Department of Metabolic Medicine, Great Ormond Street Hospital, London, UK
Ann Neurol 49:797-800. 2001....
- Leigh-like subacute necrotising encephalopathy in Yorkshire Terriers: neuropathological characterisation, respiratory chain activities and mitochondrial DNAKerstin 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...
- Outpatient anesthesia for oral surgery in a juvenile with Leigh diseaseZachary Ellis
University of Texas Dental School, Health Science Center, San Antonio, Texas, USA
Anesth Prog 52:70-3. 2005We 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...
- Defects in energy homeostasis in Leigh syndrome French Canadian variant through PGC-1alpha/LRP130 complexMarcus 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...
- Leigh syndrome associated with mitochondrial complex I deficiency due to a novel mutation in the NDUFS1 geneMiguel 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...
- Expression and functional analysis of SURF1 in Leigh syndrome patients with cytochrome c oxidase deficiencyJ 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....
- Disorders related to mitochondrial membranes: pathology of the respiratory chain and neurodegenerationS 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...
- Compound heterozygous mutations in the flavoprotein gene of the respiratory chain complex II in a patient with Leigh syndromeB 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...
- Effect of various agents on adenosine triphosphate synthesis in mitochondrial complex I deficiencyM 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...
- MRI in Leigh syndrome with SURF1 gene mutationMario Savoiardo
Ann Neurol 51:138-9. 2002
- Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 genes in mitochondrial complex I deficiencyP 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...
- Epidemiology of pediatric mitochondrial respiratory chain disorders in northwest SpainManuel 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...
- Leigh's syndromeA 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....
- Cytochrome c oxidase partial deficiency-associated Leigh disease presenting as an extrapyramidal syndromeM Cacic
Department of Pediatrics, Children s Hospital Zagreb, Croatia
J Child Neurol 16:616-9. 2001b>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...
- NDUFA2 complex I mutation leads to Leigh diseaseSaskia 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...
- Leigh Syndrome with COX deficiency and SURF1 gene mutations: MR imaging findingsAndrea 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...
- 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 syndromePaule 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...
- [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. 2002b>Leigh disease, subacute necrotizing encephalopathy, is a serious mitochondrial disorder of energy-providing metabolism...
- SURF1 gene mutations in three cases with Leigh syndrome and cytochrome c oxidase deficiencyA 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...
- A novel recurrent mitochondrial DNA mutation in ND3 gene is associated with isolated complex I deficiency causing Leigh syndrome and dystoniaEmmanuelle 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...
- De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiencyRobert 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...
- Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndromeP 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...
- Maternal segmental disomy in Leigh syndrome with cytochrome c oxidase deficiency caused by homozygous SURF1 mutationA 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...
- Late-onset Leigh syndrome in a patient with mitochondrial complex I NDUFS8 mutationsVincent 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...
- Functional and genetic studies demonstrate that mutation in the COX15 gene can cause Leigh syndromeC E Oquendo
J Med Genet 41:540-4. 2004
- Novel SURF1 mutation in a child with subacute encephalopathy and without the radiological features of Leigh SyndromeLeonardo 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...
- Recurrent de novo mitochondrial DNA mutations in respiratory chain deficiencyS 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...
- Leigh syndrome associated with a mutation in the NDUFS7 (PSST) nuclear encoded subunit of complex IR 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...
- The first nuclear-encoded complex I mutation in a patient with Leigh syndromeJ 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...
- Mitochondrial complex I deficiency caused by a deleterious NDUFA11 mutationItai 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...
- A genomewide linkage-disequilibrium scan localizes the Saguenay-Lac-Saint-Jean cytochrome oxidase deficiency to 2p16N 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...
- Multiple neonatal deaths due to a homoplasmic mitochondrial DNA mutationRobert 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...
- Molecular genetic characterization of an X-linked form of Leigh's syndromeP 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...
- Leigh disease associated with a novel mitochondrial DNA ND5 mutationRobert 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. 2002b>Leigh disease is a genetically heterogeneous, neurodegenerative disorder of childhood that is caused by defects of either the nuclear or mitochondrial genome...
- Light and electron microscopy characteristics of the muscle of patients with SURF1 gene mutations associated with Leigh diseaseM 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...
- Facial dysmorphism in Leigh syndrome with SURF-1 mutation and COX deficiencyAdnan 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...
- Decreased affinity for oxygen of cytochrome-c oxidase in Leigh syndrome caused by SURF1 mutationsPetr 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...
- Missense mutations in SURF1 associated with deficient cytochrome c oxidase assembly in Leigh syndrome patientsA 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...
- Mitochondrial DNA background modifies the bioenergetics of NARP/MILS ATP6 mutant cellsM 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...
- Diagnostic difficulties with common SURF1 mutations in patients with cytochrome oxidase-deficient Leigh syndromeR 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...
- A novel mutation in SURF1 causes skipping of exon 8 in a patient with cytochrome c oxidase-deficient leigh syndrome and hypertrichosisS 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...
- Abnormal calcium homeostasis in fibroblasts from patients with Leigh diseaseM 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...
- Three novel SURF-1 mutations in Japanese patients with Leigh syndromeYukiko Ogawa
Department of Pediatrics, School of Medicine, University of Tokushima, Tokushima, Japan
Pediatr Neurol 26:196-200. 2002....
- Two novel mutations of SURF1 in Leigh syndrome with cytochrome c oxidase deficiencyM 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...
- Leigh disease: clinical, neuroradiologic, and biochemical study of three new cases with cytochrome c oxidase deficiencyS Savasta
Division of Pediatrics and Neonatology, Istituti Ospitaleri, Cremona, Italy
J Child Neurol 16:608-13. 2001Three 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...
- Unusual clinical presentations in four cases of Leigh disease, cytochrome C oxidase deficiency, and SURF1 gene mutationsStacey K H Tay
Department of Neurology, Columbia University, New York, NY, USA
J Child Neurol 20:670-4. 2005Mutations in the SURF1 gene are the most frequent causes of Leigh disease with cytochrome c oxidase deficiency...
- Clinical and molecular features of an infant patient affected by Leigh Disease associated to m.14459G>A mitochondrial DNA mutation: a case reportDario 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...
- Hypertrichosis in patients with SURF1 mutationsElsebet Ostergaard
John F Kennedy Institute, Glostrup, Denmark
Am J Med Genet A 138:384-8. 2005....
- A Chinese girl with Leigh syndrome: effect of botulinum toxin on dystoniaT 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...
- Leigh syndrome due to compound heterozygosity of dihydrolipoamide dehydrogenase gene mutations. Description of the first E3 splice site mutationOlga 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...
- 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 syndromeSophie 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...
- New splicing-site mutations in the SURF1 gene in Leigh syndrome patientsM 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...
- A novel mutation in the human complex I NDUFS7 subunit associated with Leigh syndromeSophie 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...
- Impaired complex I assembly in a Leigh syndrome patient with a novel missense mutation in the ND6 geneCristina 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....
- Cardiomyopathy associated with neurologic disorders and mitochondrial phenotypeJose 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...
- Humanin expression in skeletal muscles of patients with chronic progressive external ophthalmoplegiaTesseki 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...
- Two new mutations in the MTATP6 gene associated with Leigh syndromeA 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...
- Bull's-eye maculopathy in an infant with Leigh diseasePhilip W Laird
Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
Am J Ophthalmol 142:186-7. 2006To report a bull's-eye maculopathy-like fundus abnormality in an infant with Leigh disease.
- Biochemical phenotypes associated with the mitochondrial ATP6 gene mutations at nt8993Alessandra 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....
- Allotopic mRNA localization to the mitochondrial surface rescues respiratory chain defects in fibroblasts harboring mitochondrial DNA mutations affecting complex I or v subunitsCrystel 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...
- G8363A mitochondrial DNA mutation is not a rare cause of Leigh syndrome - clinical, biochemical and pathological study of an affected childMaciej 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...
- The neurological evolution of Pearson syndrome: case report and literature reviewHsiu 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...
- Mutations in the ND5 subunit of complex I of the mitochondrial DNA are a frequent cause of oxidative phosphorylation diseaseM 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...
- Clinical and molecular survey in 124 Chinese patients with Leigh or Leigh-like syndromeY 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...
- SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafnessRosalba 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...
- The mitochondrial 13513G>A mutation is associated with Leigh disease phenotypes independent of complex I deficiency in muscleAriel 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...
- A previously undescribed leukodystrophy in Leigh syndrome associated with T9176C mutation of the mitochondrial ATPase 6 genePo 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...
- The mitochondrial 13513G > A mutation is most frequent in Leigh syndrome combined with reduced complex I activity, optic atrophy and/or Wolff-Parkinson-WhiteE 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...
- [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...
- Infantile mitochondrial disordersRosalba 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...
- Novel mitochondrial mutation in the ND4 gene associated with Leigh syndromeA 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...
- Analysis of mitochondrial DNA sequences in childhood encephalomyopathies reveals new disease-associated variantsAijaz 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...
- A new mitochondrial DNA mutation in ND3 gene causing severe Leigh syndrome with early lethalityMarco 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...
- [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...
- Familial mtDNA T8993C transition causing both the NARP and the MILS phenotype in the same generation. A morphological, genetic and spectroscopic studyMonica Sciacco
J Neurol 250:1498-500. 2003
- [Cytochrome c oxidase deficiency--SURF1 mutations]Etsuo Naito
Department of Pediatrics, School of Medicine, University of Tokushima
Nihon Rinsho 60:446-9. 2002
- Infantile spasms with basal ganglia MRI hypersignal may reveal mitochondrial disorder due to T8993G MT DNA mutationI 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...
- Atypical Leigh syndrome associated with the D393N mutation in the mitochondrial ND5 subunitV Petruzzella
Department of Medical Biochemistry and Medical Biology, University of Bari, Italy
Neurology 61:1017-8. 2003
- Mutation screening in patients with isolated cytochrome c oxidase deficiencySabrina 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...
- Low mutant load of mitochondrial DNA G13513A mutation can cause Leigh's diseaseDenise 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...
- [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
- [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...
- Leigh disease with mitochondrial DNA A8344G mutation: case report and brief reviewChang Yong Tsao
Department of Pediatrics, The Ohio State University, Children s Radiological Institute, Children s Hospital, Columbus, USA
J Child Neurol 18:62-4. 2003b>Leigh disease, subacute necrotizing encephalomyelopathy, is a neurodegenerative disorder often seen in infancy or childhood but rarely reported in adults...
- Complex I: Role of L Subunit in Proton TranslocationSteven 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)...
- Biosynthetic Protein Models of Heme-copper Oxidases and Nitric Oxide ReductasesYi 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. ..
- Nuclear Control of Mitochondrial Gene ExpressionGerald 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. ..
- Molecular Pathogenesis of Coenzyme Q10 DeficiencyMichio 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. ..
- ELECTROPHYSIOLOGY OF NEONATAL AND ADULT HEARTMartin Morad; Fiscal Year: 2013....
- Detection of S-(2-succino)cysteine (2SC) as a Biomarker of Mitochondrial DiseaseNorma 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. ..
- Fo Motor Mechanisms that Power FoF1 ATP SynthesisWayne 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. ..
- Pyruvate Dehydrogenase E1: Structure-Function StudiesWilliam F Furey; Fiscal Year: 2012....
- Assembly of Redox Metal Centers in Cytochrome OxidaseDennis 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. ..
- 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...
- Mitochondrial Transcription and Pediatric DiseaseNEAL 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. ..
- FACSVantage SE UpgradeRAYMOND HESTER; Fiscal Year: 2004....
- Mouse Modeling of Leigh Disease and Complex I AssemblyCarl 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 ..
- Transcriptional profiling in childhood diseasesWilliam Craigen; Fiscal Year: 2006..These results will help in counseling, the development of potential therapies, and assessing long-term outcomes. ..
- A Genetic Model of Leigh Syndrome Suppression in DrosophilaSatpal Singh; Fiscal Year: 2009..The proposed studies would provide leads on the mechanisms underlying these disorders and on possible therapeutic approaches to treat them. ..
- ATP SYNTHESIS IN MITOCHONDRIAL DISORDERSGiovanni Manfredi; Fiscal Year: 2003..Allotopic expression of the recoded wild-type genes should partially restore the APT synthetic function in mutant cells. ..
- CLINICAL RESEARCH CENTER FOR NEUROMUSCULAR DISEASESalvatore DiMauro; Fiscal Year: 2007....
- The Role of Mitochondrial DNA Alterations in CancerLee 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. ..
- Epigenetic Regulation of Mitochondiral Complex IIGerald 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. ..
- scVEGF Targeted Radiotherapy of Mammary and Colonic CancerFRANCIS 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. ..
- Transmission genetics of mammalian mitochondrial DNAEric Shoubridge; Fiscal Year: 2008..abstract_text> ..
- IMAGING APOPTOSIS IN VIVO WITH TECHNETIUM 99M ANNEXINFrancis 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. ..
- IMAGING APOPTOSIS IN VIVO WITH TECHNETIUM 99M ANNEXINFrancis Blankenberg; Fiscal Year: 2001..abstract_text> ..