title: Pathogenic mtDNA mutations causing mitochondrial myopathy: The need for muscle biopsy.
abstract: Pathogenic mitochondrial tRNA (mt-tRNA) gene mutations represent a prominent cause of primary mitochondrial DNA (mtDNA)-related disease despite accounting for only 5%-10% of the mitochondrial genome.(1,2) Although some common mt-tRNA mutations, such as the m.3243A>G mutation, exist, the majority are rare and have been reported in only a small number of cases.(3) The MT-TP gene, encoding mt-tRNA(Pro), is one of the less polymorphic mt-tRNA genes, and only 5 MT-TP mutations have been reported as a cause of mitochondrial muscle disease to date (table e-1 at Neurology.org/ng, P6-10). We report 5 patients with myopathic phenotypes, each harboring different pathogenic mutations in the MT-TP gene, highlighting the importance of MT-TP mutations as a cause of mitochondrial muscle disease and the requirement to study clinically relevant tissue.
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience (S.A.H., E.L.B., A.I.P., M.C.R., S.A., G.F., Y.S.N., D.M.T., G.S.G., R.W.T.), The Medical School, Institute of Genetic Medicine (R.H.), Newcastle University; Nuffield Department of Obstetrics and Gynaecology (J.P.), University of Oxford; Department of Neurology (M.R.R.), King's College Hospital NHS Foundation Trust, London; Departments of Neurology and Neuropathology (O.O., N.B.), Cork University Hospital, Ireland; and The Walton Centre for Neurology and Neurosurgery (C.F.D.), Liverpool, UK.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Hardy
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience (S.A.H., E.L.B., A.I.P., M.C.R., S.A., G.F., Y.S.N., D.M.T., G.S.G., R.W.T.), The Medical School, Institute of Genetic Medicine (R.H.), Newcastle University; Nuffield Department of Obstetrics and Gynaecology (J.P.), University of Oxford; Department of Neurology (M.R.R.), King's College Hospital NHS Foundation Trust, London; Departments of Neurology and Neuropathology (O.O., N.B.), Cork University Hospital, Ireland; and The Walton Centre for Neurology and Neurosurgery (C.F.D.), Liverpool, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Blakely
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience (S.A.H., E.L.B., A.I.P., M.C.R., S.A., G.F., Y.S.N., D.M.T., G.S.G., R.W.T.), The Medical School, Institute of Genetic Medicine (R.H.), Newcastle University; Nuffield Department of Obstetrics and Gynaecology (J.P.), University of Oxford; Department of Neurology (M.R.R.), King's College Hospital NHS Foundation Trust, London; Departments of Neurology and Neuropathology (O.O., N.B.), Cork University Hospital, Ireland; and The Walton Centre for Neurology and Neurosurgery (C.F.D.), Liverpool, UK.
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Purvis
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience (S.A.H., E.L.B., A.I.P., M.C.R., S.A., G.F., Y.S.N., D.M.T., G.S.G., R.W.T.), The Medical School, Institute of Genetic Medicine (R.H.), Newcastle University; Nuffield Department of Obstetrics and Gynaecology (J.P.), University of Oxford; Department of Neurology (M.R.R.), King's College Hospital NHS Foundation Trust, London; Departments of Neurology and Neuropathology (O.O., N.B.), Cork University Hospital, Ireland; and The Walton Centre for Neurology and Neurosurgery (C.F.D.), Liverpool, UK.
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Rocha
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience (S.A.H., E.L.B., A.I.P., M.C.R., S.A., G.F., Y.S.N., D.M.T., G.S.G., R.W.T.), The Medical School, Institute of Genetic Medicine (R.H.), Newcastle University; Nuffield Department of Obstetrics and Gynaecology (J.P.), University of Oxford; Department of Neurology (M.R.R.), King's College Hospital NHS Foundation Trust, London; Departments of Neurology and Neuropathology (O.O., N.B.), Cork University Hospital, Ireland; and The Walton Centre for Neurology and Neurosurgery (C.F.D.), Liverpool, UK.
authors.forename: Syeda
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience (S.A.H., E.L.B., A.I.P., M.C.R., S.A., G.F., Y.S.N., D.M.T., G.S.G., R.W.T.), The Medical School, Institute of Genetic Medicine (R.H.), Newcastle University; Nuffield Department of Obstetrics and Gynaecology (J.P.), University of Oxford; Department of Neurology (M.R.R.), King's College Hospital NHS Foundation Trust, London; Departments of Neurology and Neuropathology (O.O., N.B.), Cork University Hospital, Ireland; and The Walton Centre for Neurology and Neurosurgery (C.F.D.), Liverpool, UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Falkous
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience (S.A.H., E.L.B., A.I.P., M.C.R., S.A., G.F., Y.S.N., D.M.T., G.S.G., R.W.T.), The Medical School, Institute of Genetic Medicine (R.H.), Newcastle University; Nuffield Department of Obstetrics and Gynaecology (J.P.), University of Oxford; Department of Neurology (M.R.R.), King's College Hospital NHS Foundation Trust, London; Departments of Neurology and Neuropathology (O.O., N.B.), Cork University Hospital, Ireland; and The Walton Centre for Neurology and Neurosurgery (C.F.D.), Liverpool, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Poulton
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience (S.A.H., E.L.B., A.I.P., M.C.R., S.A., G.F., Y.S.N., D.M.T., G.S.G., R.W.T.), The Medical School, Institute of Genetic Medicine (R.H.), Newcastle University; Nuffield Department of Obstetrics and Gynaecology (J.P.), University of Oxford; Department of Neurology (M.R.R.), King's College Hospital NHS Foundation Trust, London; Departments of Neurology and Neuropathology (O.O., N.B.), Cork University Hospital, Ireland; and The Walton Centre for Neurology and Neurosurgery (C.F.D.), Liverpool, UK.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rose
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience (S.A.H., E.L.B., A.I.P., M.C.R., S.A., G.F., Y.S.N., D.M.T., G.S.G., R.W.T.), The Medical School, Institute of Genetic Medicine (R.H.), Newcastle University; Nuffield Department of Obstetrics and Gynaecology (J.P.), University of Oxford; Department of Neurology (M.R.R.), King's College Hospital NHS Foundation Trust, London; Departments of Neurology and Neuropathology (O.O., N.B.), Cork University Hospital, Ireland; and The Walton Centre for Neurology and Neurosurgery (C.F.D.), Liverpool, UK.
authors.forename: Olivia
authors.initials: O
authors.lastname: O'Mahony
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience (S.A.H., E.L.B., A.I.P., M.C.R., S.A., G.F., Y.S.N., D.M.T., G.S.G., R.W.T.), The Medical School, Institute of Genetic Medicine (R.H.), Newcastle University; Nuffield Department of Obstetrics and Gynaecology (J.P.), University of Oxford; Department of Neurology (M.R.R.), King's College Hospital NHS Foundation Trust, London; Departments of Neurology and Neuropathology (O.O., N.B.), Cork University Hospital, Ireland; and The Walton Centre for Neurology and Neurosurgery (C.F.D.), Liverpool, UK.
authors.forename: Niamh
authors.initials: N
authors.lastname: Bermingham
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience (S.A.H., E.L.B., A.I.P., M.C.R., S.A., G.F., Y.S.N., D.M.T., G.S.G., R.W.T.), The Medical School, Institute of Genetic Medicine (R.H.), Newcastle University; Nuffield Department of Obstetrics and Gynaecology (J.P.), University of Oxford; Department of Neurology (M.R.R.), King's College Hospital NHS Foundation Trust, London; Departments of Neurology and Neuropathology (O.O., N.B.), Cork University Hospital, Ireland; and The Walton Centre for Neurology and Neurosurgery (C.F.D.), Liverpool, UK.
authors.forename: Charlotte F
authors.initials: CF
authors.lastname: Dougan
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience (S.A.H., E.L.B., A.I.P., M.C.R., S.A., G.F., Y.S.N., D.M.T., G.S.G., R.W.T.), The Medical School, Institute of Genetic Medicine (R.H.), Newcastle University; Nuffield Department of Obstetrics and Gynaecology (J.P.), University of Oxford; Department of Neurology (M.R.R.), King's College Hospital NHS Foundation Trust, London; Departments of Neurology and Neuropathology (O.O., N.B.), Cork University Hospital, Ireland; and The Walton Centre for Neurology and Neurosurgery (C.F.D.), Liverpool, UK.
authors.forename: Yi Shiau
authors.initials: YS
authors.lastname: Ng
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience (S.A.H., E.L.B., A.I.P., M.C.R., S.A., G.F., Y.S.N., D.M.T., G.S.G., R.W.T.), The Medical School, Institute of Genetic Medicine (R.H.), Newcastle University; Nuffield Department of Obstetrics and Gynaecology (J.P.), University of Oxford; Department of Neurology (M.R.R.), King's College Hospital NHS Foundation Trust, London; Departments of Neurology and Neuropathology (O.O., N.B.), Cork University Hospital, Ireland; and The Walton Centre for Neurology and Neurosurgery (C.F.D.), Liverpool, UK.
authors.forename: Rita
authors.initials: R
authors.lastname: Horvath
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience (S.A.H., E.L.B., A.I.P., M.C.R., S.A., G.F., Y.S.N., D.M.T., G.S.G., R.W.T.), The Medical School, Institute of Genetic Medicine (R.H.), Newcastle University; Nuffield Department of Obstetrics and Gynaecology (J.P.), University of Oxford; Department of Neurology (M.R.R.), King's College Hospital NHS Foundation Trust, London; Departments of Neurology and Neuropathology (O.O., N.B.), Cork University Hospital, Ireland; and The Walton Centre for Neurology and Neurosurgery (C.F.D.), Liverpool, UK.
authors.forename: Doug M
authors.initials: DM
authors.lastname: Turnbull
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience (S.A.H., E.L.B., A.I.P., M.C.R., S.A., G.F., Y.S.N., D.M.T., G.S.G., R.W.T.), The Medical School, Institute of Genetic Medicine (R.H.), Newcastle University; Nuffield Department of Obstetrics and Gynaecology (J.P.), University of Oxford; Department of Neurology (M.R.R.), King's College Hospital NHS Foundation Trust, London; Departments of Neurology and Neuropathology (O.O., N.B.), Cork University Hospital, Ireland; and The Walton Centre for Neurology and Neurosurgery (C.F.D.), Liverpool, UK.
authors.forename: Grainne S
authors.initials: GS
authors.lastname: Gorman
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience (S.A.H., E.L.B., A.I.P., M.C.R., S.A., G.F., Y.S.N., D.M.T., G.S.G., R.W.T.), The Medical School, Institute of Genetic Medicine (R.H.), Newcastle University; Nuffield Department of Obstetrics and Gynaecology (J.P.), University of Oxford; Department of Neurology (M.R.R.), King's College Hospital NHS Foundation Trust, London; Departments of Neurology and Neuropathology (O.O., N.B.), Cork University Hospital, Ireland; and The Walton Centre for Neurology and Neurosurgery (C.F.D.), Liverpool, UK.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor