title: 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.
abstract: BACKGROUND
  Hippocampal sclerosis is the most common lesion in patients with mesial temporal lobe epilepsy. Recently, there has been growing evidence on the involvement of mitochondria also in sporadic forms of epilepsy. In addition, it has been increasingly argued that mitochondrial dysfunction has an important role in epileptogenesis and seizure generation in temporal lobe epilepsy. Although mtDNA polymorphisms have been identified as potential risk factors for neurological diseases, the link between homoplasmy and heteroplasmy within tissues is not clear. We investigated whether mitochondrial DNA (mtDNA) polymorphisms are involved in a case report of a patient with mesial temporal lobe epilepsy-hippocampal sclerosis (MTLE-HS).
  
  
  METHODS
  We report the whole genome mtDNA deep sequencing results and clinical features of a 36-year-old woman with MTLE-HS. We used pyrosequencing technology to sequence a whole mitochondrial genome isolated from six different regions of her brain and blood. To assess the possible role of mitochondrial DNA variations in affected tissues, we compared all specimens from different regions of the hippocampus and blood.
  
  
  RESULTS
  In total, 35 homoplasmic and 18 heteroplasmic variations have been detected in 6 different regions of the hippocampus and in blood samples. While the samples did not display any difference in homoplasmic variations, it has been shown that hippocampus regions contain more heteroplasmic variations than blood. The number of heteroplasmic variations was highest in the CA2 region of the brain and accumulated in ND2, ND4 and ND5 genes. Also, dentate and subiculum regions of the hippocampus had similar heteroplasmic variation profiles.
  
  
  CONCLUSIONS
  We present a new rare example of parallel mutation at 16223 position. Our case suggests that defects in mitochondrial function might be underlying the pathogenesis of seizures in temporal lobe epilepsy.
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Hulya
authors.initials: H
authors.lastname: Azakli
authors.forename: Candan
authors.initials: C
authors.lastname: Gurses
authors.forename: Muzaffer
authors.initials: M
authors.lastname: Arikan
authors.forename: Aydın
authors.initials: A
authors.lastname: Aydoseli
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Aras
authors.forename: Altay
authors.initials: A
authors.lastname: Sencer
authors.forename: Aysen
authors.initials: A
authors.lastname: Gokyigit
authors.forename: Bilge
authors.initials: B
authors.lastname: Bilgic
authors.forename: Duran
authors.initials: D
authors.lastname: Ustek
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D014644:Genetic Variation; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006624:Hippocampus / Q000473:pathology* / Q000601:surgery; D006801:Humans; D009422:Nervous System Diseases / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial
keywords: CA1,2,3,4; Cornu ammonis 1,2,3,4; DIPs; EEG; GTCS; HS; Hippocampal sclerosis; IQ; MRI; MTLE; Mesial temporal lobe epilepsy; PCR; PET; Parallel mutation; Pyrosequencing; SE; SNPs; Status epilepticus; Whole mtDNA sequencing; deletion-insertion polymorphisms; electroencephalography; generalized tonic clonic seizures; hippocampal sclerosis; intelligence quotient; magnetic resonance imaging; mesial temporal lobe epilepsy; mitochondrial DNA; mtDNA; polymerase chain reaction; positron emission tomography; single nucleotide polymorphisms