title: Selenoprotein biosynthesis defect causes progressive encephalopathy with elevated lactate.
abstract: OBJECTIVE
  We aimed to decipher the molecular genetic basis of disease in a cohort of children with a uniform clinical presentation of neonatal irritability, spastic or dystonic quadriplegia, virtually absent psychomotor development, axonal neuropathy, and elevated blood/CSF lactate.
  
  
  METHODS
  We performed whole-exome sequencing of blood DNA from the index patients. Detected compound heterozygous mutations were confirmed by Sanger sequencing. Structural predictions and a bacterial activity assay were performed to evaluate the functional consequences of the mutations. Mass spectrometry, Western blotting, and protein oxidation detection were used to analyze the effects of selenoprotein deficiency.
  
  
  RESULTS
  Neuropathology indicated laminar necrosis and severe loss of myelin, with neuron loss and astrogliosis. In 3 families, we identified a missense (p.Thr325Ser) and a nonsense (p.Tyr429*) mutation in SEPSECS, encoding the O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase, which was previously associated with progressive cerebellocerebral atrophy. We show that the mutations do not completely abolish the activity of SEPSECS, but lead to decreased selenoprotein levels, with demonstrated increase in oxidative protein damage in the patient brain.
  
  
  CONCLUSIONS
  These results extend the phenotypes caused by defective selenocysteine biosynthesis, and suggest SEPSECS as a candidate gene for progressive encephalopathies with lactate elevation.
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Anna-Kaisa
authors.initials: AK
authors.lastname: Anttonen
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Taru
authors.initials: T
authors.lastname: Hilander
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Tarja
authors.initials: T
authors.lastname: Linnankivi
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Isohanni
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: French
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Miljan
authors.initials: M
authors.lastname: Simonović
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Dieter
authors.initials: D
authors.lastname: Söll
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Mirja
authors.initials: M
authors.lastname: Somer
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Dorota
authors.initials: D
authors.lastname: Muth-Pawlak
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Garry L
authors.initials: GL
authors.lastname: Corthals
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Anni
authors.initials: A
authors.lastname: Laari
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Emil
authors.initials: E
authors.lastname: Ylikallio
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Marja
authors.initials: M
authors.lastname: Lähde
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Leena
authors.initials: L
authors.lastname: Valanne
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Tuula
authors.initials: T
authors.lastname: Lönnqvist
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Helena
authors.initials: H
authors.lastname: Pihko
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Anders
authors.initials: A
authors.lastname: Paetau
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Anna-Elina
authors.initials: AE
authors.lastname: Lehesjoki
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.
authors.forename: Anu
authors.initials: A
authors.lastname: Suomalainen
authors.affiliation: From the Department of Medical Genetics, Haartman Institute (A.-K.A., H.T.), Folkhälsan Institute of Genetics and Neuroscience Center (A.-K.A., A.L., A.-E.L.), Research Programs Unit, Molecular Neurology, Biomedicum Helsinki (T.H., P.I., A.L., E.Y., A.-E.L.), University of Helsinki; Departments of Clinical Genetics (A.-K.A.) and Neurology (A.S.), Helsinki University Central Hospital; Department of Pediatric Neurology (T. Linnankivi, P.I., T. Lönnqvist, H.P.), Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland; Department of Biochemistry and Molecular Genetics (R.L.F., M. Simonović), University of Illinois at Chicago; Department of Molecular Biophysics and Biochemistry (Y.L., D.S.), Yale University, New Haven, CT; Norio Centre (M. Somer), Department of Medical Genetics, Helsinki, Finland; Turku Centre for Biotechnology (D.M.-P., G.L.C.), University of Turku and Åbo Akademi University; Department of Pediatric Neurology (M.L.), South Karelia Central Hospital, Lappeenranta; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki; and Department of Pathology (A.P.), HUSLAB and University of Helsinki, Finland. G.L.C. is currently affiliated with Van't Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands. henna.tyynismaa@helsinki.fi.
authors.forename: Henna
authors.initials: H
authors.lastname: Tyynismaa
mesh_terms: D000293:Adolescent; D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D020739:Brain Diseases, Metabolic, Inborn / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000097:blood* / Q000134:cerebrospinal fluid*; D008297:Male; D009154:Mutation; D018384:Oxidative Stress / Q000235:genetics; D051140:Selenoproteins / Q000096:biosynthesis / Q000172:deficiency*
chemical_list: D051140:Selenoproteins; D019344:Lactic Acid; D000604:Amino Acyl-tRNA Synthetases; C542370:O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase, human