Michio Hirano

Summary

Affiliation: Columbia University
Country: USA

Publications

  1. pmc Effects of inhibiting CoQ10 biosynthesis with 4-nitrobenzoate in human fibroblasts
    Catarina M Quinzii
    Department of Neurology, Columbia University Medical Center, New York, New York, United States of America
    PLoS ONE 7:e30606. 2012
  2. pmc Treatment of CoQ(10) deficient fibroblasts with ubiquinone, CoQ analogs, and vitamin C: time- and compound-dependent effects
    Luis C Lopez
    Department of Neurology, Columbia University Medical Center, New York, New York, United States of America
    PLoS ONE 5:e11897. 2010
  3. ncbi A novel mutation in PNPLA2 leading to neutral lipid storage disease with myopathy
    Daniel B Ash
    Department ofNeurology, H Houston Merritt Clinical Research Center, Columbia University Medical Center, 630W168th St, P and S 4 423, New York, NY 10032, USA
    Arch Neurol 69:1190-2. 2012
  4. pmc Human coenzyme Q10 deficiency
    Catarina M Quinzii
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Neurochem Res 32:723-7. 2007
  5. pmc Apparent mtDNA heteroplasmy in Alzheimer's disease patients and in normals due to PCR amplification of nucleus-embedded mtDNA pseudogenes
    M Hirano
    Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 94:14894-9. 1997
  6. ncbi Mitochondria and the heart
    M Hirano
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York, USA
    Curr Opin Cardiol 16:201-10. 2001
  7. ncbi Defects of intergenomic communication: autosomal disorders that cause multiple deletions and depletion of mitochondrial DNA
    M Hirano
    Department of Neurology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA
    Semin Cell Dev Biol 12:417-27. 2001
  8. pmc VMA21 deficiency: a case of myocyte indigestion
    Michio Hirano
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Cell 137:213-5. 2009
  9. doi Amyotrophic lateral sclerosis with ragged-red fibers
    Michio Hirano
    Department of Neurology, Columbia University Medical Center, 3 317 Russ Berrie Medical Science Pavilion, 1150 St Nicholas Ave, New York, NY 10032, USA
    Arch Neurol 65:403-6. 2008
  10. ncbi Allogeneic stem cell transplantation corrects biochemical derangements in MNGIE
    M Hirano
    Department of Neurology, Columbia University Medical Center, 630 W 168 St, P and S 4 443, New York, NY 10032, USA
    Neurology 67:1458-60. 2006

Detail Information

Publications130 found, 100 shown here

  1. pmc Effects of inhibiting CoQ10 biosynthesis with 4-nitrobenzoate in human fibroblasts
    Catarina M Quinzii
    Department of Neurology, Columbia University Medical Center, New York, New York, United States of America
    PLoS ONE 7:e30606. 2012
    ..Our results support the concept that the degree of CoQ(10) deficiency in cells dictates the extent of ATP synthesis defects and ROS production and that 40-50% residual CoQ(10) produces maximal oxidative stress and cell death...
  2. pmc Treatment of CoQ(10) deficient fibroblasts with ubiquinone, CoQ analogs, and vitamin C: time- and compound-dependent effects
    Luis C Lopez
    Department of Neurology, Columbia University Medical Center, New York, New York, United States of America
    PLoS ONE 5:e11897. 2010
    ..However, published studies suggest that different ubiquinone analogs may produce divergent effects on oxidative phosphorylation and oxidative stress...
  3. ncbi A novel mutation in PNPLA2 leading to neutral lipid storage disease with myopathy
    Daniel B Ash
    Department ofNeurology, H Houston Merritt Clinical Research Center, Columbia University Medical Center, 630W168th St, P and S 4 423, New York, NY 10032, USA
    Arch Neurol 69:1190-2. 2012
    ..Mutations in PNPLA2, a gene encoding adipose triglyceride lipase, lead to neutral lipid storage disease with myopathy...
  4. pmc Human coenzyme Q10 deficiency
    Catarina M Quinzii
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Neurochem Res 32:723-7. 2007
    ....
  5. pmc Apparent mtDNA heteroplasmy in Alzheimer's disease patients and in normals due to PCR amplification of nucleus-embedded mtDNA pseudogenes
    M Hirano
    Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 94:14894-9. 1997
    ..We conclude that the observed heteroplasmy is an artifact...
  6. ncbi Mitochondria and the heart
    M Hirano
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York, USA
    Curr Opin Cardiol 16:201-10. 2001
    ..We describe genetic mitochondrial cardiomyopathies and briefly review mouse models and the mitochondrial theory of presbycardia...
  7. ncbi Defects of intergenomic communication: autosomal disorders that cause multiple deletions and depletion of mitochondrial DNA
    M Hirano
    Department of Neurology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA
    Semin Cell Dev Biol 12:417-27. 2001
    ..Uncovering the molecular bases of intergenomic communication defects will enhance our understanding of the mechanisms responsible for maintaining mtDNA integrity...
  8. pmc VMA21 deficiency: a case of myocyte indigestion
    Michio Hirano
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Cell 137:213-5. 2009
    ..In this issue, Ramachandran et al. (2009) report that mutations in the gene encoding the human homolog VMA21 cause the disease X-linked myopathy with excessive autophagy through an unexpected mechanism...
  9. doi Amyotrophic lateral sclerosis with ragged-red fibers
    Michio Hirano
    Department of Neurology, Columbia University Medical Center, 3 317 Russ Berrie Medical Science Pavilion, 1150 St Nicholas Ave, New York, NY 10032, USA
    Arch Neurol 65:403-6. 2008
    ..Motor neuron diseases (amyotrophic lateral sclerosis [ALS] and spinal muscular atrophy [SMA]) have been rarely associated with mitochondrial respiratory chain defects...
  10. ncbi Allogeneic stem cell transplantation corrects biochemical derangements in MNGIE
    M Hirano
    Department of Neurology, Columbia University Medical Center, 630 W 168 St, P and S 4 443, New York, NY 10032, USA
    Neurology 67:1458-60. 2006
    ..Thus, alloSCT can correct biochemical abnormalities in the blood of patients with MNGIE, but clinical efficacy remains unproven...
  11. doi Senataxin mutations and amyotrophic lateral sclerosis
    Michio Hirano
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Amyotroph Lateral Scler 12:223-7. 2011
    ..Screening for SETX mutations should be considered in patients with apparently sporadic juvenile-onset ALS, hereditary motor neuropathy, and overlap syndromes with ataxia and motor neuron disease...
  12. ncbi Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a disease of two genomes
    Michio Hirano
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA
    Neurologist 10:8-17. 2004
    ..Among the mendelian-inherited mitochondrial diseases are defects of intergenomic communication, disorders due to nDNA mutations that cause depletion and multiple deletions of mtDNA...
  13. ncbi Thymidine phosphorylase mutations cause instability of mitochondrial DNA
    Michio Hirano
    Department of Neurology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, P and S 4 443, New York, NY 10032, USA
    Gene 354:152-6. 2005
    ..We have hypothesized that the increased levels of thymidine and deoxyuridine cause mitochondrial nucleotide pool imbalances that, in turn, generate mtDNA alterations...
  14. pmc Mitochondrial neurogastrointestinal encephalomyopathy syndrome maps to chromosome 22q13.32-qter
    M Hirano
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Am J Hum Genet 63:526-33. 1998
    ..We found no evidence to implicate three candidate genes in this region, by using direct sequence analysis for DNA helicase II and by assaying enzyme activities for arylsulfatase A and carnitine palmitoyltransferase...
  15. pmc Tissue-specific oxidative stress and loss of mitochondria in CoQ-deficient Pdss2 mutant mice
    Catarina M Quinzii
    Department of Neurology, Columbia University Medical Center, New York, New York 10032, USA
    FASEB J 27:612-21. 2013
    ..Our data indicate that kidney-specific loss of mitochondria triggered by oxidative stress may be the cause of renal failure in Pdss2(kd/kd) mice...
  16. pmc Respiratory chain dysfunction and oxidative stress correlate with severity of primary CoQ10 deficiency
    Catarina M Quinzii
    Department of Neurology, Columbia University Medical Center, New York, New York 10032, USA
    FASEB J 22:1874-85. 2008
    ....
  17. doi 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...
  18. ncbi Clinical and genetic heterogeneity in progressive external ophthalmoplegia due to mutations in polymerase gamma
    Massimiliano Filosto
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Arch Neurol 60:1279-84. 2003
    ..Mutations in POLG can also cause autosomal recessive PEO, which is often associated with multisystemic disorders...
  19. ncbi ND5 is a hot-spot for multiple atypical mitochondrial DNA deletions in mitochondrial neurogastrointestinal encephalomyopathy
    Yutaka Nishigaki
    Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA
    Hum Mol Genet 13:91-101. 2004
    ..A novel aspect of the mtDNA deletions in MNGIE is the presence of microdeletions at the imperfectly homologous breakpoints...
  20. pmc Site-specific somatic mitochondrial DNA point mutations in patients with thymidine phosphorylase deficiency
    Yutaka Nishigaki
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Clin Invest 111:1913-21. 2003
    ..We hypothesize that, in patients with TP deficiency, increased levels of dThd and dUrd cause mitochondrial nucleotide pool imbalances, which, in turn, lead to mtDNA abnormalities including site-specific point mutations...
  21. pmc Reactive oxygen species, oxidative stress, and cell death correlate with level of CoQ10 deficiency
    Catarina M Quinzii
    Department of Neurology, Columbia University Medical Center, 630 W 168th St, P and S 4 423, New York, NY 10032, USA
    FASEB J 24:3733-43. 2010
    ..Our results confirm that varying degrees of CoQ(10) deficiency cause variable defects of ATP synthesis and oxidative stress. These findings may lead to more rational therapeutic strategies for CoQ(10) deficiency...
  22. pmc Unbalanced deoxynucleotide pools cause mitochondrial DNA instability in thymidine phosphorylase-deficient mice
    Luis C Lopez
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Hum Mol Genet 18:714-22. 2009
    ..These findings largely account for the pathogenesis of mitochondrial neurogastrointestinal encephalopathy (MNGIE), the first inherited human disorder of nucleoside metabolism associated with somatic DNA instability...
  23. pmc Infantile encephaloneuromyopathy and defective mitochondrial translation are due to a homozygous RMND1 mutation
    Beatriz García-Diaz
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Am J Hum Genet 91:729-36. 2012
    ..We documented that the protein localizes to mitochondria in mammalian and yeast cells. Further studies are necessary for understanding the function of this protein in mitochondrial protein translation...
  24. pmc Slowly progressive encephalopathy with hearing loss due to a mutation in the mtDNA tRNA(Leu(CUN)) gene
    Jorida Coku
    Department of Neurology, Columbia University Medical Center, New York, NY, USA
    J Neurol Sci 290:166-8. 2010
    ..Sequencing of the 22 tRNA mitochondrial genes is indicated in all unusual neurological syndromes, even in the absence of maternal inheritance...
  25. ncbi Lack of paternal inheritance of muscle mitochondrial DNA in sporadic mitochondrial myopathies
    Massimiliano Filosto
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA
    Ann Neurol 54:524-6. 2003
    ..We did not observe paternal inheritance in any of our patients...
  26. ncbi Congenital or late-onset myopathy in patients with the T14709C mtDNA mutation
    Michelangelo Mancuso
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    J Neurol Sci 228:93-7. 2005
    ..Previously described patients with the same mutation also showed congenital or late-onset myopathy. Diabetes is frequently associated with both phenotypes and is a clinical clue to the molecular diagnosis...
  27. pmc Thymidine kinase 2 (H126N) knockin mice show the essential role of balanced deoxynucleotide pools for mitochondrial DNA maintenance
    Hasan O Akman
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Hum Mol Genet 17:2433-40. 2008
    ..The H126N TK2 mouse is the first knock-in animal model of human MDS and demonstrates that the severity of TK2 deficiency in tissues may determine the organ-specific phenotype...
  28. pmc Thymidine and deoxyuridine accumulate in tissues of patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)
    Maria Lucia Valentino
    Department of Neurology, Columbia University Medical Center, 630 W 168th Street, P and S 4 443, New York, NY 10032, USA
    FEBS Lett 581:3410-4. 2007
    ..Our observations indicate that in the absence of TP activity, tissues accumulate nucleosides, which are excreted into plasma...
  29. ncbi Mitochondrial myopathy of childhood associated with mitochondrial DNA depletion and a homozygous mutation (T77M) in the TK2 gene
    Michelangelo Mancuso
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA
    Arch Neurol 60:1007-9. 2003
    ..Mutations in 2 genes involved in deoxyribonucleotide metabolism, the deoxyguanosine kinase gene (DGK) and the thymidine kinase 2 gene (TK2), have been related to this syndrome...
  30. doi Myopathy and parkinsonism in phosphoglycerate kinase deficiency
    Evangelia Sotiriou
    Department of Neurology, Columbia University Medical Center, 3 313 Russ Berrie Medical Science Pavilion, 1150 St Nicholas Avenue, New York, New York 10032, USA
    Muscle Nerve 41:707-10. 2010
    ..This case reinforces the concept that PGK deficiency is a clinically heterogeneous disorder and raises the question of a relationship between PGK deficiency and idiopathic juvenile Parkinson disease...
  31. ncbi Deoxynucleoside stress exacerbates the phenotype of a mouse model of mitochondrial neurogastrointestinal encephalopathy
    Beatriz García-Diaz
    1 Department of Neurology, Columbia University Medical Centre, New York, NY, 10032, USA
    Brain 137:1337-49. 2014
    ..Our mouse studies provide insights into the pathogenic role of thymidine and deoxyuridine imbalance in mitochondrial neurogastrointestinal encephalopathy and an excellent model to study new therapeutic approaches. ..
  32. pmc Onset and organ specificity of Tk2 deficiency depends on Tk1 down-regulation and transcriptional compensation
    Beatriz Dorado
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Hum Mol Genet 20:155-64. 2011
    ..Understanding the molecular mechanisms that allow Tk2 mutant organs to be spared may help design therapies for Tk2 deficiency...
  33. ncbi Definitive diagnosis of mitochondrial neurogastrointestinal encephalomyopathy by biochemical assays
    Ramon Marti
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA
    Clin Chem 50:120-4. 2004
    ..The clinical manifestations of MNGIE are recognizable and homogeneous, but in the early stages, the disease is often misdiagnosed. This study assesses the reliability of biochemical assays to diagnose MNGIE...
  34. ncbi Mutation in an mtDNA protein-coding gene: prenatal diagnosis aided by fetal muscle biopsy
    Sara Shanske
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    J Child Neurol 28:264-8. 2013
    ..This second girl is now 18 months old and healthy. Our observations support the concept that the pathogenic mutation in this patient appeared de novo and that fetal muscle biopsy is a useful aide in prenatal diagnosis...
  35. doi Neutral lipid storage disease with subclinical myopathy due to a retrotransposal insertion in the PNPLA2 gene
    Hasan O Akman
    Department of Neurology, Columbia University Medical Center, New York, NY, USA
    Neuromuscul Disord 20:397-402. 2010
    ..This case shows that NLSDM can be a transposon-associated disease and that massive lipid storage in muscle can present as asymptomatic hyperCKemia...
  36. pmc Heterogeneity of coenzyme Q10 deficiency: patient study and literature review
    Valentina Emmanuele
    Department of Neurology, Columbia University Medical Center, New York, New York, USA
    Arch Neurol 69:978-83. 2012
    ..Identification of CoQ(10) deficiency is important because the condition frequently responds to treatment. Causative mutations have been identified in a small proportion of patients...
  37. doi A novel tRNA(Val) mitochondrial DNA mutation causing MELAS
    Kurenai Tanji
    Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
    J Neurol Sci 270:23-7. 2008
    ..We report here a novel tRNA(Val) mutation in a 37-year-old woman with manifestations of MELAS, and compare her clinicopathological phenotype with other rare cases associated tRNA(Val) mutations...
  38. pmc A mutation in para-hydroxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency
    Catarina Quinzii
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Am J Hum Genet 78:345-9. 2006
    ..Radioisotope assays confirmed a severe defect of CoQ(10) biosynthesis in the fibroblasts of one patient. This mutation in COQ2 is the first molecular cause of primary CoQ(10) deficiency...
  39. doi Autonomic symptoms in carriers of the m.3243A>G mitochondrial DNA mutation
    Timothy Parsons
    Department of Neurology, Columbia University, 710 W 168th St, New York, NY 10032, USA
    Arch Neurol 67:976-9. 2010
    ..The m.3243A>G mutation can cause multisystem medical problems and can affect the autonomic nervous system...
  40. pmc Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations
    Luis Carlos López
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Am J Hum Genet 79:1125-9. 2006
    ..This is the first description of pathogenic mutations in PDSS2 and confirms the molecular and clinical heterogeneity of primary CoQ(10) deficiency...
  41. ncbi Longitudinal clinical follow-up of a large family with the R357P Twinkle mutation
    Carmen Paradas
    Unidad de Enfermedades Neuromusculares, Servicio de Neurologia, Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla Consejo Superior de Investigaciones Científicas Universidad de Sevilla, Seville, Spain2Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Ministry of Economy and Competitiveness, Madrid, Spain3Department of Neurology, Columbia University Medical Center, New York, New York
    JAMA Neurol 70:1425-8. 2013
    ..The aim of this study was to provide a 16-year clinical follow-up of autosomal dominant progressive external ophthalmoplegia due to the p.R357P gene mutation in PEO1...
  42. ncbi A novel mitochondrial tRNA(Leu(UUR)) mutation in a patient with features of MERRF and Kearns-Sayre syndrome
    Yutaka Nishigaki
    Department of Neurology, Columbia University College of Physicians and Surgeon, 630 West 168th Street, P and S 4 443, New York, NY 10032, USA
    Neuromuscul Disord 13:334-40. 2003
    ..The identification of yet another tRNA(Leu(UUR)) mutation reinforces the concept that this gene is a hot-spot for pathogenic mtDNA mutations...
  43. pmc Navajo neurohepatopathy is caused by a mutation in the MPV17 gene
    Charalampos L Karadimas
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Am J Hum Genet 79:544-8. 2006
    ..Identification of a single missense mutation in patients with NNH confirms that the disease is probably due to a founder effect and extends the phenotypic spectrum associated with MPV17 mutations...
  44. pmc The m.3244G>A mutation in mtDNA is another cause of progressive external ophthalmoplegia
    Evangelia Sotiriou
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Neuromuscul Disord 19:297-9. 2009
    ..The m.3244G>A mutation affects a highly conserved nucleotide in the dihydrouridine loop and has been associated with a wobble modification deficiency of the mutant tRNA...
  45. doi Protean phenotypic features of the A3243G mitochondrial DNA mutation
    Petra Kaufmann
    Department of Neurology, The Neurological Institute, Columbia University Medical Center, New York, NY 10032, USA
    Arch Neurol 66:85-91. 2009
    ....
  46. ncbi Novel mitochondrial DNA ND5 mutation in a patient with clinical features of MELAS and MERRF
    Ali B Naini
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Arch Neurol 62:473-6. 2005
    ....
  47. doi Recurrent myoglobinuria in a sporadic patient with a novel mitochondrial DNA tRNA(Ile) mutation
    Valentina Emmanuele
    Department of Neurology, Columbia University Medical Center, New York, NY, USA
    J Neurol Sci 303:39-42. 2011
    ..Single-fiber analysis revealed significantly higher levels of the mutation in COX-deficient (65%) than in normal fibers (45%). This novel mutation has to be added to the molecular causes of recurrent myoglobinuria...
  48. pmc Coenzyme Q and mitochondrial disease
    Catarina M Quinzii
    Department of Neurology, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA
    Dev Disabil Res Rev 16:183-8. 2010
    ..In vitro and in vivo studies are necessary to further understand the pathogenesis of the disease and to develop more effective therapies...
  49. ncbi Elevated plasma deoxyuridine in patients with thymidine phosphorylase deficiency
    Ramon Marti
    Department of Neurology, Columbia University College of Physicians and Surgeons, P and S 4 443, 630 West 168th Street, New York, NY 10032, USA
    Biochem Biophys Res Commun 303:14-8. 2003
    ..05 microM) in both TP mutation carriers and controls. The dramatic accumulation of dUrd may contribute to nucleotide pool imbalances and, together with the increased levels of dThd, is likely to contribute to the pathogenesis of MNGIE...
  50. ncbi Early-onset familial parkinsonism due to POLG mutations
    Guido Davidzon
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Ann Neurol 59:859-62. 2006
    ..To define the molecular etiology of early-onset parkinsonism and peripheral neuropathy...
  51. pmc Biochemical and genetic analysis of Leigh syndrome patients in Korea
    Jong Hee Chae
    Department of Neurology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, P and S 4 443, New York, NY, USA
    Brain Dev 30:387-90. 2008
    ..Although a limited study based in a single tertiary medical center, our findings suggest that isolated complex I deficiency may be the most common cause of Leigh syndrome in Korea...
  52. ncbi Mitochondrial diseases
    Tuan H Vu
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA
    Neurol Clin 20:809-39, vii-viii. 2002
    ..In this article, the authors, we summarize the principles of mitochondrial genetics and discuss the common phenotypes, general diagnostic approach, and possible therapeutic venues for these fascinating disorders...
  53. pmc MERRF and Kearns-Sayre overlap syndrome due to the mitochondrial DNA m.3291T>C mutation
    Valentina Emmanuele
    Department of Neurology, Columbia University Medical Center, 630 West 168th Street, P and S 4 423, New York, New York 10032, USA
    Muscle Nerve 44:448-51. 2011
    ..This mutation has been reported with MELAS, myopathy, and deafness with cognitive impairment. This is the first description with a MERRF/KSS syndrome...
  54. ncbi POLG mutations and Alpers syndrome
    Guido Davidzon
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Ann Neurol 57:921-3. 2005
    ..We conclude that AHS should be included in the clinical spectrum of mtDNA depletion and is often associated with POLG mutations, which can cause either multiple mtDNA deletions or mtDNA depletion...
  55. pmc Complex I deficiency primes Bax-dependent neuronal apoptosis through mitochondrial oxidative damage
    Celine Perier
    Department of Neurology, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 102:19126-31. 2005
    ..This molecular scenario may have far-reaching implications for the development of effective neuroprotective therapies for these incurable illnesses...
  56. pmc Identical mitochondrial DNA deletion in a woman with ocular myopathy and in her son with pearson syndrome
    Sara Shanske
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA
    Am J Hum Genet 71:679-83. 2002
    ..We conclude that, although the vast majority of single large-scale deletions in mtDNA are sporadic, in rare cases, single deletions can be transmitted through the germline...
  57. pmc Clinical and genetic spectrum of mitochondrial neurogastrointestinal encephalomyopathy
    Caterina Garone
    Department of Neurology, Columbia University Medical Centre, New York, NY 10032, USA
    Brain 134:3326-32. 2011
    ....
  58. pmc X-linked dominant scapuloperoneal myopathy is due to a mutation in the gene encoding four-and-a-half-LIM protein 1
    Catarina M Quinzii
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Am J Hum Genet 82:208-13. 2008
    ..This is the first report, to our knowledge, of X-linked dominant SP myopathy and the first human mutation in FHL1...
  59. pmc CoQ10 deficiency diseases in adults
    Catarina M Quinzii
    Department of Neurology, Columbia University Medical Center, P and S 4 420, 630 West 168th Street, New York, NY 10032, USA
    Mitochondrion 7:S122-6. 2007
    ..Mutations in the CoQ10 biosynthetic genes, COQ2 and PDSS2, have been identified in children with the infantile form of CoQ10 deficiency; however, the molecular genetic bases of adult-onset CoQ10 deficiency remains undefined...
  60. pmc Neonatal mitochondrial encephaloneuromyopathy due to a defect of mitochondrial protein synthesis
    Claudia C Ferreiro-Barros
    Department of Neurology, Columbia University, New York, NY, USA
    J Neurol Sci 275:128-32. 2008
    ..Our studies indicate that the patient has a novel autosomal recessive defect of mitochondrial protein synthesis...
  61. doi Branching enzyme deficiency: expanding the clinical spectrum
    Carmen Paradas
    Department of Neurology, Columbia University Medical Center, New York, New York2Unidad de Enfermedades Neuromusculares, Servicio de Neurologia, Hospital Universitario Virgen del Rocio, Instituto de Biomedicina de Sevilla, Consejo Superior de Investigación
    JAMA Neurol 71:41-7. 2014
    ..A better definition of this new clinical entity is needed to facilitate diagnosis...
  62. pmc CoQ(10) deficiencies and MNGIE: two treatable mitochondrial disorders
    Michio Hirano
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Biochim Biophys Acta 1820:625-31. 2012
    ..Two examples of treatable mitochondrial disorders are coenzyme Q(10) (CoQ(10) or ubiquinone) deficiency and mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)...
  63. ncbi Alteration of nucleotide metabolism: a new mechanism for mitochondrial disorders
    Ramon Marti
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Clin Chem Lab Med 41:845-51. 2003
    ..However, alterations of mtDNA have not yet been established in this disorder. Future studies are likely to reveal additional diseases and provide further insight into this new subject...
  64. pmc Mutations in coenzyme Q10 biosynthetic genes
    Salvatore DiMauro
    Department of Neurology, Columbia University Medical Center, New York, New York, USA
    J Clin Invest 117:587-9. 2007
    ..Awareness of CoQ10 deficiency is important because individuals with primary or secondary variants may benefit from oral CoQ10 supplementation...
  65. ncbi Late-onset MNGIE due to partial loss of thymidine phosphorylase activity
    Ramon Marti
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Ann Neurol 58:649-52. 2005
    ..This report demonstrates a direct relationship between the biochemical defects and clinical phenotypes in MNGIE and supports the notion that reduction of dThd and dUrd accumulation or TP replacement could be useful therapy for MNGIE...
  66. pmc Therapeutic prospects for mitochondrial disease
    Eric A Schon
    Department of Neurology, Columbia University Medical Center, New York, NY, USA
    Trends Mol Med 16:268-76. 2010
    ..Among these are techniques to upregulate mitochondrial biogenesis, enhance organellar fusion and fission, "shift heteroplasmy" and eliminate the burden of mutant mtDNAs via cytoplasmic transfer...
  67. pmc A novel mutation in the tRNAIle gene (MTTI) affecting the variable loop in a patient with chronic progressive external ophthalmoplegia (CPEO)
    Andres Berardo
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Neuromuscul Disord 20:204-6. 2010
    ..Like tRNA(Leu(UUR)), tRNA(Ile) appears to be a "hot spot" for mtDNA mutations causing CPEO...
  68. ncbi Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical, biochemical, and genetic features of an autosomal recessive mitochondrial disorder
    M Hirano
    Department of Neurology, Columbia Presbyterian Medical Center, College of Physicians and Surgeons, Columbia University, New York, NY
    Neurology 44:721-7. 1994
    ..Two patients had isolated complex I defects, and one had normal respiratory chain function. Southern blot analysis revealed multiple deletions of mitochondrial DNA in four of eight patients...
  69. pmc Primary and secondary CoQ(10) deficiencies in humans
    Catarina M Quinzii
    Department of Neurology, Columbia University Medical Center, New York, USA
    Biofactors 37:361-5. 2011
    ..Respiratory chain defects, ROS production, and apoptosis variably contribute to the pathogenesis of primary CoQ(10) deficiencies...
  70. ncbi Primary coenzyme Q10 deficiency and the brain
    Ali Naini
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Biofactors 18:145-52. 2003
    ..Daily oral administration of CoQ10 led to substantial increases of CoQ10 concentrations only in blood and liver. Of the four regions of one human brain studied, cerebellum again had the lowest CoQ10y concentration...
  71. ncbi A polymorphic polymerase
    Salvatore DiMauro
    Department of Neurology, Columbia University Medical Center New York, NY, USA
    Brain 129:1637-9. 2006
  72. ncbi A novel ND3 mitochondrial DNA mutation in three Korean children with basal ganglia lesions and complex I deficiency
    Jong Hee Chae
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Pediatr Res 61:622-4. 2007
    ..This study underscores the importance of screening mtDNA-encoded respiratory chain structural genes, including ND3, in pediatric patients with unexplained encephalopathies...
  73. pmc A diagnostic algorithm for metabolic myopathies
    Andres Berardo
    Department of Neurology, Columbia University Medical Center, 630 West 168th Street, P and S 4 423, New York, NY 10032, USA
    Curr Neurol Neurosci Rep 10:118-26. 2010
    ....
  74. ncbi Mitochondrial encephalomyopathies: an update
    Salvatore DiMauro
    Department of Neurology, Columbia University Medical Center, College of Physicians and Surgeons, Room 4 420, 630 West 168th Street, New York, NY 10032, USA
    Neuromuscul Disord 15:276-86. 2005
    ....
  75. ncbi Novel cell lines derived from adult human ventricular cardiomyocytes
    Mercy M Davidson
    Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    J Mol Cell Cardiol 39:133-47. 2005
    ..These cell lines are potentially useful in vitro models to study developmental regulation of cardiomyocytes in normal and pathological states...
  76. ncbi MRI of five patients with mitochondrial neurogastrointestinal encephalomyopathy
    William S Millar
    Department of Radiology, New York Presbyterian Hospital, Columbia Presbyterian Center, 177 Fort Washington Avenue, Milstein Hospital Bldg, Rm 3 105, New York, NY 10032, USA
    AJR Am J Roentgenol 182:1537-41. 2004
    ..The purpose of this study was to retrospectively review MR images of the brain in five patients diagnosed with mitochondrial neurogastrointestinal encephalomyopathy...
  77. pmc LAMP-2 deficiency (Danon disease)
    S Di Mauro
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Acta Myol 26:79-82. 2007
  78. ncbi Mitochondria in neuromuscular disorders
    S DiMauro
    Department of Neurology, H Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, Columbia University College of Physicians and Surgeons, 4 420, 630 West 168th Street, New York, NY 10032, USA
    Biochim Biophys Acta 1366:199-210. 1998
    ..Uncertainties about pathogenesis extend to the process of cell death, although excitotoxicity in neurons and apoptosis in muscle seem to have important roles...
  79. ncbi Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial
    P Kaufmann
    Department of Neurology, Columbia University, New York 10032, USA
    Neurology 66:324-30. 2006
    ..To evaluate the efficacy of dichloroacetate (DCA) in the treatment of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS)...
  80. doi Pathogenesis and treatment of mitochondrial disorders
    Salvatore DiMauro
    Department of Neurology, Columbia University Medical Center, 3 313 Russ Berrie Medical Science Pavilion, New York, NY 10032, USA
    Adv Exp Med Biol 652:139-70. 2009
    ..g. boosting ATP production or scavenging ROS), which are inconsistently and incompletely effective, but can be safe and helpful...
  81. ncbi Approaches to the treatment of mitochondrial diseases
    Salvatore DiMauro
    Department of Neurology, Columbia University Medical Center, 4 420 College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, USA
    Muscle Nerve 34:265-83. 2006
    ..Preventive therapy through genetic counseling and prenatal diagnosis is becoming increasingly important for nuclear DNA-related disorders...
  82. ncbi Pathogenesis of the deafness-associated A1555G mitochondrial DNA mutation
    Carla Giordano
    Department of Neurology, College of Physicians and Surgeons, Columbia University, Room 5 431, 630 West 168th Street, Columbia, NY 10032, USA
    Biochem Biophys Res Commun 293:521-9. 2002
    ..The decrease did not correlate with the rate of synthesis or stability of mitochondrial DNA-encoded subunits or respiratory chain activity. Further studies are required to determine the underlying biochemical defect...
  83. ncbi Does linezolid cause lactic acidosis by inhibiting mitochondrial protein synthesis?
    Lluis Palenzuela
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, USA
    Clin Infect Dis 40:e113-6. 2005
    ..The toxicity may have been caused by linezolid binding to mitochondrial 16S rRNA. Genetic polymorphisms may have contributed to the toxicity in 2 patients...
  84. ncbi Mitochondrial DNA depletion and dGK gene mutations
    Leonardo Salviati
    Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA
    Ann Neurol 52:311-7. 2002
    ..The patient with the missense mutations had isolated liver failure and responded well to liver transplantation, which may be a therapeutic option in selected cases...
  85. ncbi Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder
    I Nishino
    Columbia University College of Physicians and Surgeons, Department of Neurology, 630 West 168 Street, P and S 4 443, New York, NY 10032, USA
    Science 283:689-92. 1999
    ..The pathogenic mechanism may be related to aberrant thymidine metabolism, leading to impaired replication or maintenance of mtDNA, or both...
  86. pmc Human CoQ10 deficiencies
    C M Quinzii
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Biofactors 32:113-8. 2008
    ..In many patients with CoQ10 deficiencies, the causative molecular genetic defects remain unknown; therefore, it is likely that mutations in additional genes will be identified as causes of CoQ10 deficiencies...
  87. ncbi Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation
    C M Quinzii
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Neurology 64:539-41. 2005
    ..The authors' observations indicate that CoQ10 deficiency may contribute to the pathogenesis of AOA1...
  88. ncbi Thymidine phosphorylase deficiency causes MNGIE: an autosomal recessive mitochondrial disorder
    M Hirano
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Nucleosides Nucleotides Nucleic Acids 23:1217-25. 2004
    ..MNGIE was the first molecularly characterized genetic disorder caused by abnormal mitochondrial nucleoside/nucleotide metabolism. Future studies are likely to reveal further insight into this expanding group of diseases...
  89. ncbi Tissue-specific expression and chromosome assignment of genes specifying two isoforms of subunit VIIa of human cytochrome c oxidase
    E Arnaudo
    H Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Disorders, Columbia University College of Physicians and Surgeons, New York, NY 10032
    Gene 119:299-305. 1992
    ..In contrast, COXVIIa-L cDNA probes hybridized to fragments from two COX7AL loci, on chromosomes 4 and 14...
  90. ncbi Exercise-induced muscle "burning," fatigue, and hyper-CKemia: mtDNA T10010C mutation in tRNA(Gly)
    Y Nishigaki
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Neurology 58:1282-5. 2002
    ..Muscle biopsy showed ragged red fibers and reduced activities of mitochondrial respiratory chain enzyme complexes I, III, and IV. Analysis of mitochondrial DNA revealed a heteroplasmic T10010C mutation in the transfer RNA glycine gene...
  91. ncbi MNGIE: from nuclear DNA to mitochondrial DNA
    I Nishino
    Department of Neurology, Columbia University, New York, NY 10032, USA
    Neuromuscul Disord 11:7-10. 2001
    ..The identification of the MNGIE gene has allowed us to classify MNGIE as a disease of nucleoside dysmetabolism. We may be entering a new era of research on mitochondrial nucleoside metabolism...
  92. ncbi Altered thymidine metabolism due to defects of thymidine phosphorylase
    Antonella Spinazzola
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Biol Chem 277:4128-33. 2002
    ..We hypothesize that excess thymidine alters mitochondrial nucleoside and nucleotide pools leading to impaired mitochondrial DNA replication, repair, or both. Therapies to reduce thymidine levels may be beneficial to MNGIE patients...
  93. ncbi Metabolic myopathies
    Michio Hirano
    Department of Neurology, Columbia Presbyterian Medical Center, New York, New York 10032, USA
    Adv Neurol 88:217-34. 2002
  94. ncbi Reversion of mtDNA depletion in a patient with TK2 deficiency
    M R Vila
    Department of Neurology, Columbia University College of Physicians and Surgeons New York, NY, USA
    Neurology 60:1203-5. 2003
    ..This report extends the phenotypic expression of primary TK2 deficiency and suggests that factors other than TK2 may modify expression of the clinical phenotype in patients with MDS syndrome...
  95. ncbi Mitochondrial DNA depletion: mutations in thymidine kinase gene with myopathy and SMA
    M Mancuso
    Department of Neurology, P and S Building 5 431, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA
    Neurology 59:1197-202. 2002
    ..Mutations in TK2 have been associated with the myopathic form of MDS, and mutations in dGK with the hepatoencephalopathic form...
  96. ncbi Mitochondrial involvement in Alzheimer's disease
    E Bonilla
    Departments of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Biochim Biophys Acta 1410:171-82. 1999
    ..On the other hand, the role(s) of somatic cell or maternally inherited mtDNA mutations in the pathogenesis of mitochondrial dysfunction in AD are still controversial...
  97. ncbi Clinical course of a cohort in the Cuban epidemic optic and peripheral neuropathy
    D S Mojon
    Department of Ophthalmology, Columbia University College of Physicians and Surgeons, New York, NY, USA
    Neurology 48:19-22. 1997
    ..Patients with poor recovery or further deterioration should be evaluated for other factors, including poor vitamin therapy compliance and alternative diagnoses...
  98. ncbi Molecular and genetic characterization of sarcospan: insights into sarcoglycan-sarcospan interactions
    R H Crosbie
    Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City 52242, USA
    Hum Mol Genet 9:2019-27. 2000
    ..These findings are important as they contribute to a greater understanding of the structural determinants required for proper sarcoglycan-sarcospan expression and function...
  99. ncbi Cerebellar ataxia and coenzyme Q10 deficiency
    C Lamperti
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA
    Neurology 60:1206-8. 2003
    ..Associated symptoms included seizures, developmental delay, mental retardation, and pyramidal signs. These findings confirm the existence of an ataxic presentation of CoQ10 deficiency, which may be responsive to CoQ10 supplementation...
  100. ncbi Cerebral lactic acidosis correlates with neurological impairment in MELAS
    P Kaufmann
    Department of Neurology, Columbia University, New York, NY 10032, USA
    Neurology 62:1297-302. 2004
    ..To evaluate the role of chronic cerebral lactic acidosis in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)...
  101. ncbi Differential expression of genes specifying two isoforms of subunit VIa of human cytochrome c oxidase
    G M Fabrizi
    H Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Disorders, Columbia University College of Physicians and Surgeons, New York, NY 10032
    Gene 119:307-12. 1992
    ..The cDNA specifying COX VIa-M is a prime candidate for use in investigations of Mendelian-inherited COX deficiencies with primary involvement of muscle...

Research Grants13

  1. Pathogenesis of a Novel Limb-Girdle Muscular Dystrophy
    Michio Hirano; Fiscal Year: 2003
    ..For the patients, achieving the proposed goals will allow more accurate prenatal diagnosis, genetic counseling, and perhaps contribute to more rational therapies in the future. ..
  2. Pathogenesis of a Novel Limb-Girdle Muscular Dystrophy
    Michio Hirano; Fiscal Year: 2002
    ..For the patients, achieving the proposed goals will allow more accurate prenatal diagnosis, genetic counseling, and perhaps contribute to more rational therapies in the future. ..
  3. Pathogenesis of a Novel Limb-Girdle Muscular Dystrophy
    Michio Hirano; Fiscal Year: 2002
    ..For the patients, achieving the proposed goals will allow more accurate prenatal diagnosis, genetic counseling, and perhaps contribute to more rational therapies in the future. ..
  4. Pathogenesis of a Novel Limb-Girdle Muscular Dystrophy
    Michio Hirano; Fiscal Year: 2001
    ..For the patients, achieving the proposed goals will allow more accurate prenatal diagnosis, genetic counseling, and perhaps contribute to more rational therapies in the future. ..
  5. Pathogenesis of a Novel Limb-Girdle Muscular Dystrophy
    Michio Hirano; Fiscal Year: 2002
    ..For the patients, achieving the proposed goals will allow more accurate prenatal diagnosis, genetic counseling, and perhaps contribute to more rational therapies in the future. ..
  6. Molecular Pathogenesis of Coenzyme Q10 Deficiency
    Michio Hirano; Fiscal Year: 2010
    ....
  7. Molecular Pathogenesis and Treatment of MNGIE
    Michio Hirano; Fiscal Year: 2010
    ..We propose to study a mouse model to understand and to treat this disorder. Studies of MNGIE may be relevant to a variety of human diseases, aging, comprehending stability of genetic material, and possibly neurodegenerative diseases. ..
  8. Pathogenesis of a Novel Limb-Girdle Muscular Dystrophy
    Michio Hirano; Fiscal Year: 2003
    ..For the patients, achieving the proposed goals will allow more accurate prenatal diagnosis, genetic counseling, and perhaps contribute to more rational therapies in the future. ..
  9. Molecular Pathogenesis of Coenzyme Q10 Deficiency
    Michio Hirano; Fiscal Year: 2009
    ....