title: Respiratory chain deficiency in nonmitochondrial disease.
abstract: OBJECTIVE
  In this study, we report 5 patients with heterogeneous phenotypes and biochemical evidence of respiratory chain (RC) deficiency; however, the molecular diagnosis is not mitochondrial disease.
  
  
  METHODS
  The reported patients were identified from a cohort of 60 patients in whom RC enzyme deficiency suggested mitochondrial disease and underwent whole-exome sequencing.
  
  
  RESULTS
  Five patients had disease-causing variants in nonmitochondrial disease genes ORAI1, CAPN3, COLQ, EXOSC8, and ANO10, which would have been missed on targeted next-generation panels or on MitoExome analysis.
  
  
  CONCLUSIONS
  Our data demonstrate that RC abnormalities may be secondary to various cellular processes, including calcium metabolism, neuromuscular transmission, and abnormal messenger RNA degradation.
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
authors.forename: Angela
authors.initials: A
authors.lastname: Pyle
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Nightingale
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
authors.forename: Helen
authors.initials: H
authors.lastname: Griffin
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
authors.forename: Angela
authors.initials: A
authors.lastname: Abicht
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
authors.forename: Janbernd
authors.initials: J
authors.lastname: Kirschner
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
authors.forename: Ivo
authors.initials: I
authors.lastname: Baric
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
authors.forename: Mario
authors.initials: M
authors.lastname: Cuk
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Douroudis
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
authors.forename: Lea
authors.initials: L
authors.lastname: Feder
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
authors.forename: Markus
authors.initials: M
authors.lastname: Kratz
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
authors.forename: Birgit
authors.initials: B
authors.lastname: Czermin
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kleinle
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
authors.forename: Mauro
authors.initials: M
authors.lastname: Santibanez-Koref
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
authors.forename: Veronika
authors.initials: V
authors.lastname: Karcagi
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
authors.forename: Elke
authors.initials: E
authors.lastname: Holinski-Feder
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
authors.forename: Rita
authors.initials: R
authors.lastname: Horvath