title: Frequency of mitochondrial transfer RNA mutations and deletions in 225 patients presenting with respiratory chain deficiencies.
abstract: OBJECTIVE
  To evaluate the frequency of pathogenic mtDNA transfer RNA mutations and deletions in biochemically demonstrable respiratory chain (RC) deficiencies in paediatric and adult patients.
  
  
  METHODS
  We screened for deletions and sequenced mitochondrial transfer RNA genes in skeletal muscle DNA from 225 index patients with clinical symptoms suggestive of a mitochondrial disorder and with biochemically demonstrable RC deficiency in skeletal muscle.
  
  
  RESULTS
  We found pathogenic mitochondrial DNA mutations in 29% of the patients. The detection rate was significantly higher in adults (48%) than in the paediatric group (18%). Only one pathogenic mutation was detected in the neonatal group. In addition, we describe seven novel transfer RNA sequence variations with unknown pathogenic relevance (six homoplasmic and one heteroplasmic) and 13 homoplasmic polymorphisms. One heteroplasmic transfer RNA(Leu(UUR)) A>G mutation at position 3274 is associated with a distinct neurological syndrome.
  
  
  CONCLUSIONS
  We provide an estimation of the frequency of mitochondrial transfer RNA mutations and deletions in paediatric and adult patients with respiratory chain deficiencies.
authors.affiliation: Metabolic Disease Centre Munich-Schwabing and Institute of Clinical Chemistry, Diagnostic Molecular Biology, and Mitochondrial Genetics, Munich, Germany. Michaela.Jaksch@lrz.uni-muenchen.de
authors.forename: M
authors.initials: M
authors.lastname: Jaksch
authors.forename: S
authors.initials: S
authors.lastname: Kleinle
authors.forename: C
authors.initials: C
authors.lastname: Scharfe
authors.forename: T
authors.initials: T
authors.lastname: Klopstock
authors.forename: D
authors.initials: D
authors.lastname: Pongratz
authors.forename: J
authors.initials: J
authors.lastname: Müller-Höcker
authors.forename: K D
authors.initials: KD
authors.lastname: Gerbitz
authors.forename: S
authors.initials: S
authors.lastname: Liechti-Gallati
authors.forename: H
authors.initials: H
authors.lastname: Lochmuller
authors.forename: R
authors.initials: R
authors.lastname: Horvath
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004579:Electron Transport / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000235:genetics / Q000473:pathology; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012343:RNA, Transfer / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D000077278:RNA, Mitochondrial; D012313:RNA; D012343:RNA, Transfer