Taiwanese Journal of Obstetrics and Gynecology
Volume 45, Issue 3 , Pages 201-207 , September 2006

Genotype-Phenotype Correlation of Maternally Inherited Disorders due to Mutations in Mitochondrial DNA

  • Peterus Thajeb

      Affiliations

    • Department of Neurology, Taipei, Taiwan
    • Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    • Department of National Yang-Ming University School of Medicine, Taipei, Taiwan
    • Department of Taipei Medical University, Taipei, Taiwan
    • Corresponding Author InformationCorrespondence to: Dr Peterus Thajeb, P.O. Box Nei-Hu 6-30, Taipei City 11499, Taiwan
    • ,
  • Daofu Dai

      Affiliations

    • Department of Pathology, School of Medicine, University of Washington, Seattle, USA
    • ,
  • Ming-Fu Chiang

      Affiliations

    • Department of Neurosurgery, Taipei, Taiwan
    • ,
  • Woei-Cherng Shyu

      Affiliations

    • Department of Neurology, Neuromedical Scientific Center, Tzu-Chi University, Hualien, Taiwan

,Accepted 31 March 2006.

References 

  1. Nass MM , Nass S . Intramitochondrial fibers with DNA characteristics. I. Fixation and electron staining reactions . J Cell Biol . 1963;19:593–611
  2. Anderson S , Bankier AT , Barrell BG , et al.   Sequence and organization of human mitochondrial genome . Nature . 1981;290:457–465
  3. Shoffner JM , Wallace DC . Oxidative phosphorylation diseases. Disorders of two genomes . In:  Harris H ,  Hirschhorn K editor. Advances in Human Genetics . 19: Plenum; 1990;p. 267–330
  4. Shoffner JM , Lott MT , Lezza AM , Seibel P , Ballinger SW , Wallace DC . Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNALysmutation . Cell . 1990;61:931–937
  5. Hammans SR , Sweeney MG , Brockington M , et al.   The mitochondrial DNA transfer RNA(Lys)A to G(3243) mutation and the syndrome of myoclonic epilepsy with ragged-red fibers (MERRF). Relationship of clinical phenotype to proportion of mutant mitochondrial DNA . Brain . 1993;116:617–632
  6. Hammans SR , Sweeney MG , Hanna MG , Brockington M , Morgan-Hughes JA , Harding AE . The mitochondrial DNA transfer RNALeu(UUR) A to G(3243) mutation. A clinical and genetic study . Brain . 1995;118:721–734
  7. Chinnery PF , Howell N , Lightowlers RN , Turnbull DM . Molecular pathology of MELAS and MERRF. The relationship between mutation load and clinical phenotypes . Brain . 1997;120:1713–1721
  8. Tzen CY , Thajeb P , Wu TY , Chen SC . MELAS with point mutations involving tRNALeu (A3243G) and tRNAGlu (14693G) . Muscle Nerve . 2003;28:575–581
  9. Thajeb P, Ma YS, Tzen CY, Chuang CK, Wu TY, Chen SC, et al. Oculopharyngeal somatic myopathy in a patient with a novel large-scale 3,399 bp deletion and a homoplasmic T5814C transition of the mitochondrial DNA . Clin Neurol Neurosurg . 2006;108:407–410
  10. Pavlakis SG , Phillips PC , DiMauro S , deVivo DC , Rowland LP . Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes: a distinctive clinical syndrome . Ann Neurol . 1984;16:481–488
  11. Ciafaloni E , Ricci E , Shanske S , et al.   MELAS: clinical features, biochemistry, and molecular genetics . Ann Neurol . 1992;31:391–398
  12. Abe K . Cerebral lactic acidosis correlates with neurological impairment in MELAS . Neurology . 2004;63:2458
  13. Thajeb P , Huang KM , Chi EY , Shih CC , Su ML , Huang JS . Koshevnikov syndrome in a patient with MELAS plus syndrome: electron microscopic and neuroimage studies . Chin Med J (Taipei) . 1997;110:726–730
  14. Finsterer J , Kopsa W . Basal ganglia calcification in mitochondrial disorders . Metab Brain Dis . 2005;20:219–226
  15. Parry A , Matthews PM . Roles for imaging in understanding the pathophysiology, clinical evaluation, and management of patients with mitochondrial disease . J Neuroimaging . 2003;13:293–302
  16. Apostolova LG , White M , Moore SA , Davis PH . Deep white matter pathologic features in watershed regions: a novel pattern of central nervous system involvement in MELAS . Arch Neurol . 2005;62:1154–1156
  17. Lerman-Sagie T , Leshinsky-Silver E , Watemberg N , Luckman Y , Lev D . White matter involvement in mitochondrial diseases . Mol Genet Metab . 2005;84:127–136
  18. McFarland R , Taylor RW , Turnbull DM . The neurology of mitochondrial DNA disease . Lancet Neurology . 2002;1:343–351
  19. Peng NJ , Liu RS , Li JY , et al.   Increased cerebral blood flow in MELAS shown by Tc-99m HMPAO brain SPECT . Neuroradiology . 2000;42:26–29
  20. Thajeb P , Wu MC , Shih BF , Tzen CY , Chiang MF , Yuan RY . Brain SPECT studies in patients with A3243G mutation of the mitochondrial DNA . Ann N Y Acad Sci . 2005;1042:48–54
  21. Goto Y , Nonaka I , Horai S . A mutation in the tRNA (Leu) (UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies . Nature . 1990;348:651–653
  22. Fang W , Huang CC , Lee CC , et al.   Ophthalmologic manifestations in MELAS syndrome . Arch Neurol . 1993;50:977–980
  23. Macmillan C , Lach B , Shoubridge EA . Variable distribution of mutant mitochondrial DNAs tRNA(Leu[3243]) in tissues of symptomatic relatives with MELAS: the role of mitotic segregation . Neurology . 1993;43:1586–1590
  24. Liou CW , Huang CC , Chee EC , et al.   MELAS syndrome correlation between clinical features and molecular genetic analysis . Acta Neurol Scand . 1994;90:354–359
  25. Zhang Y , Li JF , Wang FY , Li CX . The study of A3243G and G13513A mitochondria DNA point mutation in patients with cerebral infarction . Chin Med J (Beijing) . 2001;114:129–135
  26. Tokunago M , Mita S , Sakuta R , Nonaka I , Araki S . Increased mitochondrial DNA in blood vessels and ragged-red fibers in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) . Ann Neurol . 1993;33:275–280
  27. Shoffner JM , Wallace DC . Oxidative phosphorylation diseases . In:  Scriver CR ,  Beaudet AL ,  Sly WS ,  Valle D editor. The Metabolic and Molecular Basis of Inherited Disease . New York: McGraw-Hill; 1995;p. 1535–1609
  28. Kobayashi Y , Ichihashi K , Ohta S , et al.   The mutant mitochondrial genes in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) were selectively amplified through generations . J Inherit Metab Dis . 1992;15:803–808
  29. Silvestri G , Ciafaloni E , Santorelli FM , et al.   Clinical features associated with the A to G transition at nucleotide 8344 of mtDNA (“MERRF mutation”) . Neurology . 1993;43:1200–1206
  30. Tanno Y , Yoneda M , Tanaka K , et al.   Uniform tissue distribution of tRNA(Lys) mutation in mitochondrial DNA in MERRF patients . Neurology . 1993;43:1198–1200
  31. Servidei S . Mitochondrial encephalomyopathies: gene mutation . Neuromuscul Disord . 2004;14:107–116
  32. DiMauro S , Gurgel-Giannetti J . The expanding phenotype of mitochondrial myopathy . Curr Opin Neurol . 2005;18:538–542
  33. Hsu CC , Chuang YH , Tsai JL , et al.   CPEO and carnitine deficiency overlapping in MELAS syndrome . Acta Neurol Scand . 1995;92:252–255
  34. Kearns TP , Sayre GP . Retinitis pigmentosa, external ophthalmoplegia and complete heart block . Ophthalmology . 1958;60:280–289
  35. Seneca S , Verhelst H , deMeirleir L , et al.   A new mitochondrial point mutation in the transfer RNA(Leu) gene in a patient with a clinical phenotype resembling Kearns-Sayre syndrome . Arch Neurol . 2001;58:1113–1118
  36. Moraes CT , Zeviani M , Schon EA , Hickman RO , Vlcek BW , DiMauro S . Mitochondrial DNA deletion in a girl with manifestations of Kearns-Sayre and Lowe syndromes: an example of phenotypic mimicry? . Am J Med Genet . 1991;41:301–305
  37. Leigh D . Subacute necrotizing encephalomyelopathy in an infant . J Neurol Neurosurg Psychiatry . 1951;14:216–221
  38. Christensen E , Melchior JC , Plum P . Infantile chronic necrotizing encephalopathy . Acta Paediatr . 1963;52:304–312
  39. Pincus JH . Subacute necrotizing encephalomyelopathy (Leigh's disease): a consideration of clinical features and etiology . Dev Med Child Neurol . 1972;14:87–101
  40. Sipe JC . Leigh's syndrome: the adult form of subacute necrotizing encephalomyelopathy with predilection for the brainstem . Neurology . 1973;23:1030–1038
  41. Hommes FA , Polman HA , Reerink JD . Leigh's encephalomyelopathy: an inborn error of gluconeogenesis . Arch Dis Child . 1968;43:423–426
  42. Van Maldergem L , Trijbels F , DiMauro S , et al.   Co-enzyme Q-responsive Leigh's encephalopathy in two sisters . Ann Neurol . 2002;52:750–754
  43. Mattiazzi M , Vijayvergiya C , Gajewski CD , et al.   The mtDNA T8993G (NARP) mutation results in an impairment of oxidative phosphorylation that can be improved by antioxidants . Hum Mol Genet . 2004;13:869–879
  44. Wilson CJ , Wood NW , Leonard JV , Surtees R , Rahman S . Mitochondrial DNA point mutation T9176C in Leigh syndrome . J Child Neurol . 2000;15:830–833
  45. Jiang YW , Qin J , Yuan Y , Qi Y , Wu XR . Neuropathologic and clinical features in eight Chinese patients with Leigh disease . J Child Neurol . 2002;17:450–452
  46. Lev D , Yanoov-Sharav M , Watemberg N , Leshinsky-Silver E , Lerman-Sagie T . White matter abnormalities in Leber's hereditary optic neuropathy due to the 3460 mitochondrial DNA mutation . Eur J Paediatr Neurol . 2002;6:121–123
  47. Morimoto N , Nagano I , Deguchi K , et al.   Leber hereditary optic neuropathy with chorea and dementia resembling Huntington disease . Neurology . 2004;63:2451–2452
  48. Leonard JV , Schapira AHV . Mitochondrial respiratory chain disorders I: mitochondrial DNA defects . Lancet . 2000;355:299–304
  49. Finsterer J , Jarius C , Eichberger  , Jaksch M . Phenotype variability in 130 adult patients with respiratory chain disorder . J Inher Metab Dis . 2001;24:560–576
  50. Man PY , Turnbull DM , Chinnery PF . Leber hereditary optic neuropathy . J Med Genet . 2002;39:162–169
  51. Howell N, Miller NR, Mackey DA, Arnold A, Herrnstadt C, Williams IM, et al. Lightning strikes twice: Leber hereditary optic neuropathy families with two pathogenic mtDNA mutations . J Neuroophthalmol . 2002;22:262–269
  52. Valentino ML , Barboni P , Ghelli A , et al.   The ND1 gene of complex 1 is a mutational hotspot for Leber's hereditary optic neuropathy . Ann Neurol . 2004;56:631–641
  53. Lodi R , Carelli V , Cortelli P , et al.   Phosphorous MR spectroscopy shows a tissue specific in vivo distribution of biochemical expression of the G3460A mutation in Leber's hereditary optic neuropathy . J Neurol Neurosurg Psychiatry . 2002;72:805–807
  54. Hirano M , Silvestri G , Blake DM , et al.   Mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE): clinical, biochemical, and genetic features of an autosomal recessive mitochondrial disorder . Neurology . 1994;44:721–727
  55. Nishino I , Spinazzola A , Hirano M . Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder . Science . 1999;283:689–692
  56. Said G , Lacroix C , Plante-Bordeneuve V , et al.   Clinicopathological aspects of the neuropathy of neurogastrointestinal encephalomyopathy (MNGIE) in four patients including two with a Charcot-Marie-Tooth presentation . J Neurol . 2005;252:655–662
  57. Nishigaki Y , Marti R , Hirano M . ND5 is a hotspot for multiple atypical mitochondrial DNA deletions in mitochondrial neurogastrointestinal encephalomyopathy . Hum Mol Genet . 2004;13:91–101
  58. Vissing J , Ravn K , Danielsen ER , et al.   Multiple mtDNA deletions with features of MNGIE . Neurology . 2002;59:926–929
  59. McFarland R , Taylor RW , Turnbull DM . The neurology of mitochondrial DNA disease . Lancet Neurology . 2002;1:343–351
  60. Zeviani M , Gellera C , Antozzi C , et al.   Maternally inherited myopathy and cardiomyopathy: association with mutation in mitochondrial DNA tRNA (Leu) (UUR) . Lancet . 1991;338:143–147
  61. Dalakas MC , Illa I , Pezeshkpour GH , et al.   Mitochondrial myopathy caused by long-term zidovudine therapy . N Engl J Med . 1990;322:1098
  62. Campos Y , Martin MA , Lorenzo G , Aparicio M , Cabello A , Arenas J . Sporadic ME/MELAS overlap syndrome associated with the 3243 tRNA(Leu(UUR)) mutation of mitochondrial DNA . Muscle Nerve . 1996;19:187–190
  63. Pulkes T , Eunson L , Patterson V , et al.   The mitochondrial DNA G13513A transition in ND5 is associated with LHON/MELAS overlap syndrome and may be a frequent cause of MELAS . Ann Neurol . 1999;46:916–919
  64. Crimi M , Galbiati S , Moroni I , et al.   A missense mutation in the mitochondrial ND5 gene associated with a Leigh-MELAS overlap syndrome . Neurology . 2003;60:1857–1861
  65. Mancuso M , Ferraris S , Pancrudo J , et al.   New DGK gene mutations in the hepatocerebral form of mitochondrial DNA depletion syndrome . Arch Neurol . 2005;62:745–747
  66. Ciafaloni E , Ricci E , Servidei S , et al.   Widespread tissue distribution of a tRNALeu(UUR) mutation in the mitochondrial DNA of a patient with MELAS syndrome . Neurology . 1991;41:1663–1664
  67. Shiraiwa N , Ishii A , Iwamoto H , Mizusawa H , Kagawa Y , Ohta S . Content of mutant mitochondrial DNA and organ dysfunction in a patient with a MELAS subgroup of mitochondrial encephalomyopathies . J Neurol Sci . 1993;120:174–179
  68. Tanno Y , Yoneda M , Tanaka K , et al.   Quantitation of heteroplasmy of mitochondrial tRNA(Leu(UUR)) gene using PCR-SSCP . Muscle Nerve . 1995;18:1390–1397
  69. Holt IJ , Harding AE , Petty PK , Morgan-Hughes JA . A new mitochondrial disease associated with mitochondrial DNA heteroplasmy . Am J Hum Genet . 1990;46:428–433

PII: S1028-4559(09)60225-4

doi: 10.1016/S1028-4559(09)60225-4

Taiwanese Journal of Obstetrics and Gynecology
Volume 45, Issue 3 , Pages 201-207 , September 2006

Article Tools