title: Assigning pathogenicity to mitochondrial tRNA mutations: when "definitely maybe" is not good enough.
abstract: Some mutations in mitochondrial tRNA (mt-tRNA) genes cause devastating disease, whereas others have no clinical consequences. We understand little of the factors determining the pathogenicity of specific mt-tRNA mutations, making prediction of clinical outcome extremely difficult. Using extensive sequence databases, we compared the characteristics of neutral variations with those of pathogenic mutations. We recommend that the location of the proposed mutation within the secondary structure of the mt-tRNA molecule and the disruption it causes to Watson-Crick base pairing should be considered when assessing the pathological significance of a novel mt-tRNA mutation.
authors.affiliation: Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle-upon-Tyne NE2 4HH, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: McFarland
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Elson
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.forename: Neil
authors.initials: N
authors.lastname: Howell
authors.forename: Douglass M
authors.initials: DM
authors.lastname: Turnbull
mesh_terms: D006801:Humans; D009154:Mutation; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012343:RNA, Transfer / Q000235:genetics*
chemical_list: D000077278:RNA, Mitochondrial; D012313:RNA; D012343:RNA, Transfer