Tissue-specific involvement of multiple mitochondrial DNA deletions in familial mitochondrial myopathy.

It is still uncertain how deleted mitochondrial DNA (mtDNA) is distributed to each tissue during development, although deletions of mtDNA have been extensively observed in various pathologic conditions. This paper presents two Japanese siblings with progressive external ophthalmoplegia exhibiting multiple mtDNA deletions. In one patient, similar multiple mtDNA deletions were found in skeletal muscle specimens as well as in the spinal cord but not in the myocardium, liver or leukocytes. A similar deletion pattern was found in the skeletal muscle but not in the leukocytes of the other patient. The results suggest the complex mechanism to generate, expand and eliminate the deleted mtDNA in humans.

[1]  E. Shoubridge,et al.  Tissue-specific selection for different mtDNA genotypes in heteroplasmic mice , 1997, Nature Genetics.

[2]  E. Holme,et al.  Clonal expansion of mitochondrial DNA with multiple deletions in autosomal dominant progressive external ophthalmoplegia , 1996, Annals of neurology.

[3]  S. Dimauro,et al.  Multiple mitochondrial DNA deletions in sporadic inclusion body myositis: A study of 56 patients , 1996, Annals of neurology.

[4]  Y. Goto,et al.  Detection of DNA fragments encompassing the deletion junction of mitochondrial genome. , 1996, Biochemical and Biophysical Research Communications - BBRC.

[5]  S. Dimauro,et al.  Multiple mitochondria1 DNA deletions associated with autosomal recessive ophthalmoplegia and severe cardiomyopathy , 1996, Neurology.

[6]  L. Peltonen,et al.  An autosomal locus predisposing to multiple deletions of mtDNA on chromosome 3p. , 1996, American journal of human genetics.

[7]  E. Holme,et al.  Mitochondrial DNA Deletions in Muscle Fibers in Inclusion Body Myositis , 1995, Journal of neuropathology and experimental neurology.

[8]  M. Akaike,et al.  Mitochondrial encephalomyopathy with autosomal dominant inheritance: A clinical and genetic entity of mitochondrial diseases , 1995, Muscle & nerve.

[9]  W. Kaufmann,et al.  Diagnoses of neuronal ceroid-lipofuscinosis by immunochemical methods. , 1995, American journal of medical genetics.

[10]  L. Peltonen,et al.  An autosomal locus predisposing to deletions of mitochondrial DNA , 1995, Nature Genetics.

[11]  E. Shoubridge,et al.  Late‐onset mitochondrial myopathy , 1995, Annals of neurology.

[12]  X. Estivill,et al.  Multiple deletions of mtDNA in two brothers with sideroblastic anemia and mitochondrial myopathy and in their asymptomatic mother. , 1994, Human molecular genetics.

[13]  Y. Kagawa,et al.  Widespread tissue distribution of multiple mitochondrial DNA deletions in familial mitochondrial myopathy , 1994, Muscle & nerve.

[14]  P. Tonali,et al.  Ophthalmoplegia, demyelinating neuropathy, leukoencephalopathy, myopathy, and gastrointestinal dysfunction with multiple deletions of mitochondrial DNA: A mitochondrial multisystem disorder in search of a name , 1994, Muscle & nerve.

[15]  S. Dimauro,et al.  Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) , 1994, Neurology.

[16]  L. Peltonen,et al.  Multiple deletions of mitochondrial DNA in several tissues of a patient with severe retarded depression and familial progressive external ophthalmoplegia. , 1992, The Journal of clinical investigation.

[17]  P. Nagley,et al.  Multiple mitochondrial DNA deletions in an elderly human individual , 1992, FEBS letters.

[18]  A. Munnich,et al.  Maternally inherited duplication of the mitochondrial genome in a syndrome of proximal tubulopathy, diabetes mellitus, and cerebellar ataxia. , 1992, American journal of human genetics.

[19]  E. Holme,et al.  Lack of transmission of deleted mtDNA from a woman with Kearns-Sayre syndrome to her child. , 1992, American journal of human genetics.

[20]  E. Bertini,et al.  Dominantly inherited mitochondrial myopathy with multiple deletions of mitochondrial DNA , 1991, Neurology.

[21]  T. Ozawa,et al.  Mitochondrial DNA deletions in inherited recurrent myoglobinuria , 1991, Annals of neurology.

[22]  A. Munnich,et al.  Autosomal dominant deletions of the mitochondrial genome in a case of progressive encephalomyopathy. , 1991, American journal of human genetics.

[23]  N. Bresolin,et al.  Nucleus-driven multiple large-scale deletions of the human mitochondrial genome: a new autosomal dominant disease. , 1990, American journal of human genetics.

[24]  I. Kanazawa,et al.  Multiple deletions in mitochondrial DNA at direct repeats of non-D-loop regions in cases of familial mitochondrial myopathy. , 1989, Biochemical and biophysical research communications.

[25]  S. Dimauro,et al.  An autosomal dominant disorder with multiple deletions of mitochondrial DNA starting at the D-loop region , 1989, Nature.

[26]  G. J. Edwards.  Stable clocks and the theory of relativity , 1981, Nature.