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Mitochondrial DNA has three major variations
Gene 554 (2015) 254
Contents lists available at ScienceDirect
Gene journal homepage: www.elsevier.com/locate/gene
Mitochondrial DNA has three major variations
Dear Editor We read the article by Azakli et al. (2013) entitled as “Whole mitochondrial DNA variations in hippocampal surgical specimens and blood samples with high-throughput sequencing: A case of mesial temporal lobe epilepsy with hippocampal sclerosis” with great interest. In this study, authors aimed to investigate whether mitochondrial DNA (mtDNA) polymorphisms are involved in a patient with mesial temporal lobe epilepsy-hippocampal sclerosis (MTLE-HS). With this aim, they made whole genome sequencing of mtDNA and established clinical features of a 36-year-old woman with MTLE-HS. Authors used pyrosequencing technology to sequence whole mitochondrial genome using DNA isolated from six different regions of a patient's brain and blood. They found 35 homoplasmic and 18 heteroplasmic variations in 6 different regions of the hippocampus and in blood samples and they showed that hippocampus regions contain more heteroplasmic variations than blood. They concluded their study as defects in mitochondrial function might be underlying the pathogenesis of seizures in temporal lobe epilepsy. This is a well written and highly scientific paper, however; we just want to make some constructive additions. In this study, point mutations have been analyzed for mitochondrial variations. But, there are three major variations of mtDNA (DiMauro and Bonilla, 2004): i. point mutations, ii. mtDNA deletions and
http://dx.doi.org/10.1016/j.gene.2014.07.036 0378-1119/© 2014 Published by Elsevier B.V.
iii. mtDNA depletions. Anyone of these alterations might be the cause of mitochondrial dysfunction. Mitochondrial encephalomyopathy, lactic acidosis and stroke like syndrome occur by a point mutation. But, Kearn–Sayre syndrome is caused by large scale deletions of mtDNA. On the one hand, Alpers' disease is caused by the combination of the deletion of one allele and a mutation in the remaining allele of POLG gene. On the other hand, mtDNA depletions underlie other human disorders too. We saw that the authors have considered just point mutations. There are papers in literature that indicate that mtDNA deletions or depletions may cause gliosis in the brain (Cohen and Naviaux, 2010). We just wanted to add to this highly scientific article that the mtDNA variations other than point mutations may also have a role in mitochondrial dysfunction, hippocampal sclerosis and epilepsy. References Azakli, H.,Gurses, C.,Arikan, M.,Aydoseli, A.,Aras, Y.,Sencer, A.,Gokyigit, A.,Bilgic, B.,Ustek, D., 2013. Whole mitochondrial DNA variations in hippocampal surgical specimens and blood samples with high-throughput sequencing: a case of mesial temporal lobe epilepsy with hippocampal sclerosis. Gene 529 (1), 190–194 (Oct 15). Cohen, B.H., Naviaux, R.K., 2010. The clinical diagnosis of POLG disease and other mitochondrial DNA depletion disorders. Methods 51 (4), 364–373 (Aug). DiMauro, S.,Bonilla, E., 2004. Mitochondrial encephalomyopathies. In: Engel, A.G., FranziniArmstrong, C. (Eds.), Myology. vol. II. McGraw Hill, Philadelphia, pp. 1623–1676.
20 May 2014
Contents lists available at ScienceDirect
Gene journal homepage: www.elsevier.com/locate/gene
Mitochondrial DNA has three major variations
Dear Editor We read the article by Azakli et al. (2013) entitled as “Whole mitochondrial DNA variations in hippocampal surgical specimens and blood samples with high-throughput sequencing: A case of mesial temporal lobe epilepsy with hippocampal sclerosis” with great interest. In this study, authors aimed to investigate whether mitochondrial DNA (mtDNA) polymorphisms are involved in a patient with mesial temporal lobe epilepsy-hippocampal sclerosis (MTLE-HS). With this aim, they made whole genome sequencing of mtDNA and established clinical features of a 36-year-old woman with MTLE-HS. Authors used pyrosequencing technology to sequence whole mitochondrial genome using DNA isolated from six different regions of a patient's brain and blood. They found 35 homoplasmic and 18 heteroplasmic variations in 6 different regions of the hippocampus and in blood samples and they showed that hippocampus regions contain more heteroplasmic variations than blood. They concluded their study as defects in mitochondrial function might be underlying the pathogenesis of seizures in temporal lobe epilepsy. This is a well written and highly scientific paper, however; we just want to make some constructive additions. In this study, point mutations have been analyzed for mitochondrial variations. But, there are three major variations of mtDNA (DiMauro and Bonilla, 2004): i. point mutations, ii. mtDNA deletions and
http://dx.doi.org/10.1016/j.gene.2014.07.036 0378-1119/© 2014 Published by Elsevier B.V.
iii. mtDNA depletions. Anyone of these alterations might be the cause of mitochondrial dysfunction. Mitochondrial encephalomyopathy, lactic acidosis and stroke like syndrome occur by a point mutation. But, Kearn–Sayre syndrome is caused by large scale deletions of mtDNA. On the one hand, Alpers' disease is caused by the combination of the deletion of one allele and a mutation in the remaining allele of POLG gene. On the other hand, mtDNA depletions underlie other human disorders too. We saw that the authors have considered just point mutations. There are papers in literature that indicate that mtDNA deletions or depletions may cause gliosis in the brain (Cohen and Naviaux, 2010). We just wanted to add to this highly scientific article that the mtDNA variations other than point mutations may also have a role in mitochondrial dysfunction, hippocampal sclerosis and epilepsy. References Azakli, H.,Gurses, C.,Arikan, M.,Aydoseli, A.,Aras, Y.,Sencer, A.,Gokyigit, A.,Bilgic, B.,Ustek, D., 2013. Whole mitochondrial DNA variations in hippocampal surgical specimens and blood samples with high-throughput sequencing: a case of mesial temporal lobe epilepsy with hippocampal sclerosis. Gene 529 (1), 190–194 (Oct 15). Cohen, B.H., Naviaux, R.K., 2010. The clinical diagnosis of POLG disease and other mitochondrial DNA depletion disorders. Methods 51 (4), 364–373 (Aug). DiMauro, S.,Bonilla, E., 2004. Mitochondrial encephalomyopathies. In: Engel, A.G., FranziniArmstrong, C. (Eds.), Myology. vol. II. McGraw Hill, Philadelphia, pp. 1623–1676.
20 May 2014