title: A novel MTTT mutation m.15933G > A revealed in analysis of mitochondrial DNA in patients with suspected mitochondrial disease.
abstract: BACKGROUND
  Mitochondrial diseases present with variable multi-organ symptoms. Common disease-causing mutations in mitochondrial DNA (mtDNA) are regularly screened in diagnostic work-up, but novel mutations may remain unnoticed.
  
  
  METHODS
  Patients (N = 66) with a clinical suspicion of mitochondrial disease were screened for their mtDNA coding region using conformation sensitive gel electrophoresis and sequencing. Long-PCR was used to detect deletions followed by POLG1 sequencing in patients with multiple deletions.
  
  
  RESULTS
  We discovered three novel mtDNA variants that included m.8743G > C, m.11322A > G and m.15933G > A. The novel MTTT variant m.15933G > A is suggested to be pathogenic. Analysis revealed also multiple mtDNA deletions in two patients and five nonsynonymous variants that were putatively pathogenic according to in-silico prediction algorithms. In addition, a rare haplogroup H associated m.7585_7586insT variant was discovered.
  
  
  CONCLUSIONS
  Among patients with a suspected mitochondrial disease, a novel MTTT variant m.15933G > A was discovered and is suggested to be pathogenic. In addition, several putatively pathogenic nonsynonymous variants and rare variants were found. These findings highlight the importance of coding region mtDNA screening among patients with clinical features suggesting a mitochondrial disease, but who lack the common mitochondrial disease mutations.
authors.affiliation: Research Unit of Clinical Neuroscience, Neurology, University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland. heidi.soini@oulu.fi.|Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland. heidi.soini@oulu.fi.|Department of Neurology, Oulu University Hospital, P.O. Box 20, FI-90029 OYS, Oulu, Finland. heidi.soini@oulu.fi.|PEDEGO Research Unit, Pediatrics, University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland. heidi.soini@oulu.fi.
authors.forename: Heidi K
authors.initials: HK
authors.lastname: Soini
authors.affiliation: Research Unit of Clinical Neuroscience, Neurology, University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.|Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.|Department of Neurology, Oulu University Hospital, P.O. Box 20, FI-90029 OYS, Oulu, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Väisänen
authors.affiliation: Research Unit of Clinical Neuroscience, Neurology, University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.|Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.|Department of Neurology, Oulu University Hospital, P.O. Box 20, FI-90029 OYS, Oulu, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Kärppä
authors.affiliation: Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.|PEDEGO Research Unit, Pediatrics, University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.|Department of Pediatrics, Oulu University Hospital, P.O. Box 23, FI-90029 OYS, Oulu, Finland.
authors.forename: Reetta
authors.initials: R
authors.lastname: Hinttala
authors.affiliation: Research Unit of Clinical Neuroscience, Neurology, University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.|Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.|Department of Neurology, Oulu University Hospital, P.O. Box 20, FI-90029 OYS, Oulu, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Kytövuori
authors.affiliation: Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.|Department of Clinical Genetics, Oulu University Hospital, P.O. Box 23, FI-90029 OYS, Oulu, Finland.|PEDEGO Research Unit, Clinical Genetics, University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.
authors.forename: Jukka S
authors.initials: JS
authors.lastname: Moilanen
authors.affiliation: Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.|PEDEGO Research Unit, Pediatrics, University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.|Department of Pediatrics, Oulu University Hospital, P.O. Box 23, FI-90029 OYS, Oulu, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Uusimaa
authors.affiliation: Research Unit of Clinical Neuroscience, Neurology, University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.|Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.|Department of Neurology, Oulu University Hospital, P.O. Box 20, FI-90029 OYS, Oulu, Finland.
authors.forename: Kari
authors.initials: K
authors.lastname: Majamaa
mesh_terms: D001483:Base Sequence; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames / Q000235:genetics; D010802:Phylogeny; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human
keywords: Insertion; MTTT; Mitochondrial disease; Multiple deletions; POLG1; mtDNA