Ghent University Academic Bibliography

Advanced

Mitochondrial mosaics in the liver of 3 infants with mtDNA defects

Frank Roels UGent, PATRICK VERLOO UGent, François Eyskens, Baudouin François, Sara Seneca, Boel De Paepe UGent, Jean-Jacques Martin, VALERIE MEERSSCHAUT UGent, Marleen Praet UGent and Emmanuel Scalais, et al. (2009) BMC Clinical Pathology. 9(4). p.1-12
abstract
Three unrelated infants showed a mitochondrial mosaic in the liver after staining for COX activity, i.e. hepatocytes with strongly reactive mitochondria were found adjacent to cells with many negative, or barely reactive, mitochondria. Deficiency was most severe in the patient diagnosed with Pearson syndrome. Ragged-red fibers were absent in muscle biopsies of all patients. Enzyme biochemistry was not diagnostic in muscle, fibroblasts and lymphocytes. Blue native gel electrophoresis of liver tissue, but not of muscle, demonstrated a decreased activity of complex IV; in both muscle and liver subcomplexes of complex V were seen. Immunocytochemistry of complex IV confirmed the mosaic pattern in two livers, but not in fibroblasts. MRI of the brain revealed severe white matter cavitation in the Pearson case, but only slight cortical atrophy in the Alpers-Huttenlocher patient, and a normal image in the 3rd. MtDNA in leucocytes showed a common deletion in 50% of the mtDNA molecules of the Pearson patient. In the patient diagnosed with Alpers-Huttenlocher syndrome, mtDNA was depleted for 60% in muscle. In the 3rd patient muscular and hepatic mtDNA was depleted for more than 70%. Mutations in the nuclear encoded gene of POLG were subsequently found in both the 2nd and 3rd patients. Conclusion Histoenzymatic COX staining of a liver biopsy is fast and yields crucial data about the pathogenesis; it indicates whether mtDNA should be assayed. Each time a mitochondrial disorder is suspected and muscle data are non-diagnostic, a liver biopsy should be recommended. Mosaics are probably more frequent than observed until now. A novel pathogenic mutation in POLG is reported. Tentative explanations for the mitochondrial mosaics are, in one patient, unequal partition of mutated mitochondria during mitoses, and in two others, an interaction between products of several genes required for mtDNA maintenance.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
Pearson syndrome/Alpers-Huttenlocher syndrome/muscle/fibroblasts/brain/MRI/cytochrome oxidase activity/diaminobenzidine stain/electron microscopy/immunocytochemistry/blue native PAGE/OXPHOS activities/mtDNA depletion/POLG/
journal title
BMC Clinical Pathology
BMC clin. pathol.
editor
Melissa Norton, MD, Jigisha Patel, MRCP and Scott Edmunds, PhD
volume
9
issue
4
pages
1 - 12
ISSN
1472-6890
DOI
10.1186/1472-6890-9-4
language
English
UGent publication?
yes
classification
A2
copyright statement
I have retained and own the full copyright for this publication
VABB id
c:vabb:280904
VABB type
VABB-1
id
715962
handle
http://hdl.handle.net/1854/LU-715962
date created
2009-07-10 18:24:36
date last changed
2015-06-17 11:16:27
@article{715962,
  abstract     = {Three unrelated infants showed a mitochondrial mosaic in the liver after staining for COX activity, i.e. hepatocytes with strongly reactive mitochondria were found adjacent to cells with many negative, or barely reactive, mitochondria. Deficiency was most severe in the patient diagnosed with Pearson syndrome. Ragged-red fibers were absent in muscle biopsies of all patients. Enzyme biochemistry was not diagnostic in muscle, fibroblasts and lymphocytes. Blue native gel electrophoresis of liver tissue, but not of muscle, demonstrated a decreased activity of complex IV; in both muscle and liver subcomplexes of complex V were seen. Immunocytochemistry of complex IV confirmed the mosaic pattern in two livers, but not in fibroblasts. MRI of the brain revealed severe white matter cavitation in the Pearson case, but only slight cortical atrophy in the Alpers-Huttenlocher patient, and a normal image in the 3rd. MtDNA in leucocytes showed a common deletion in 50\% of the mtDNA molecules of the Pearson patient. In the patient diagnosed with Alpers-Huttenlocher syndrome, mtDNA was depleted for 60\% in muscle. In the 3rd patient muscular and hepatic mtDNA was depleted for more than 70\%. Mutations in the nuclear encoded gene of POLG were subsequently found in both the 2nd and 3rd patients.
Conclusion
Histoenzymatic COX staining of a liver biopsy is fast and yields crucial data about the pathogenesis; it indicates whether mtDNA should be assayed. Each time a mitochondrial disorder is suspected and muscle data are non-diagnostic, a liver biopsy should be recommended. Mosaics are probably more frequent than observed until now. A novel pathogenic mutation in POLG is reported.
Tentative explanations for the mitochondrial mosaics are, in one patient, unequal partition of mutated mitochondria during mitoses, and in two others, an interaction between products of several genes required for mtDNA maintenance.},
  author       = {Roels, Frank and VERLOO, PATRICK and Eyskens, Fran\c{c}ois and Fran\c{c}ois, Baudouin and Seneca, Sara and De Paepe, Boel and Martin, Jean-Jacques and MEERSSCHAUT, VALERIE and Praet, Marleen and Scalais, Emmanuel and Espeel, Marc and Smet, Jo{\'e}l and Van Goethem, Gert and Van Coster, Rudy},
  editor       = {Norton, MD, Melissa and Patel, MRCP, Jigisha and Edmunds, PhD, Scott},
  issn         = {1472-6890},
  journal      = {BMC Clinical Pathology},
  keyword      = {Pearson syndrome/Alpers-Huttenlocher syndrome/muscle/fibroblasts/brain/MRI/cytochrome oxidase activity/diaminobenzidine stain/electron microscopy/immunocytochemistry/blue native PAGE/OXPHOS activities/mtDNA depletion/POLG/},
  language     = {eng},
  number       = {4},
  pages        = {1--12},
  title        = {Mitochondrial mosaics in the liver of 3 infants with mtDNA defects},
  url          = {http://dx.doi.org/10.1186/1472-6890-9-4},
  volume       = {9},
  year         = {2009},
}

Chicago
Roels, Frank, PATRICK VERLOO, François Eyskens, Baudouin François, Sara Seneca, Boel De Paepe, Jean-Jacques Martin, et al. 2009. “Mitochondrial Mosaics in the Liver of 3 Infants with mtDNA Defects.” Ed. Melissa Norton, MD, Jigisha Patel, MRCP, and Scott Edmunds, PhD. BMC Clinical Pathology 9 (4): 1–12.
APA
Roels, F., VERLOO, P., Eyskens, F., François, B., Seneca, S., De Paepe, B., Martin, J.-J., et al. (2009). Mitochondrial mosaics in the liver of 3 infants with mtDNA defects. (M. Norton, MD, J. Patel, MRCP, & S. Edmunds, PhD, Eds.)BMC Clinical Pathology, 9(4), 1–12.
Vancouver
1.
Roels F, VERLOO P, Eyskens F, François B, Seneca S, De Paepe B, et al. Mitochondrial mosaics in the liver of 3 infants with mtDNA defects. Norton, MD M, Patel, MRCP J, Edmunds, PhD S, editors. BMC Clinical Pathology. 2009;9(4):1–12.
MLA
Roels, Frank, PATRICK VERLOO, François Eyskens, et al. “Mitochondrial Mosaics in the Liver of 3 Infants with mtDNA Defects.” Ed. Melissa Norton, MD, Jigisha Patel, MRCP, & Scott Edmunds, PhD. BMC Clinical Pathology 9.4 (2009): 1–12. Print.