Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency</title><author><name sortKey="Olsen, Rikke K J" sort="Olsen, Rikke K J" uniqKey="Olsen R" first="Rikke K. J." last="Olsen">Rikke K. J. Olsen</name><affiliation><nlm:aff id="aff1">Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and University Hospital, 8200 Aarhus N, Denmark</nlm:aff></affiliation></author><author><name sortKey="Ko A Kova, Eliska" sort="Ko A Kova, Eliska" uniqKey="Ko A Kova E" first="Eliška" last="Ko A Ková">Eliška Ko A Ková</name><affiliation><nlm:aff id="aff2">Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Giancaspero, Teresa A" sort="Giancaspero, Teresa A" uniqKey="Giancaspero T" first="Teresa A." last="Giancaspero">Teresa A. Giancaspero</name><affiliation><nlm:aff id="aff4">Department of Biosciences, Biotechnology, and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, Italy</nlm:aff></affiliation></author><author><name sortKey="Mosegaard, Signe" sort="Mosegaard, Signe" uniqKey="Mosegaard S" first="Signe" last="Mosegaard">Signe Mosegaard</name><affiliation><nlm:aff id="aff1">Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and University Hospital, 8200 Aarhus N, Denmark</nlm:aff></affiliation></author><author><name sortKey="Boczonadi, Veronika" sort="Boczonadi, Veronika" uniqKey="Boczonadi V" first="Veronika" last="Boczonadi">Veronika Boczonadi</name><affiliation><nlm:aff id="aff5">Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK</nlm:aff></affiliation></author><author><name sortKey="Matakovi, Lavinija" sort="Matakovi, Lavinija" uniqKey="Matakovi L" first="Lavinija" last="Matakovi">Lavinija Matakovi</name><affiliation><nlm:aff id="aff6">Department of Paediatrics, Paracelsus Medical University, SALK Salzburg, 5020 Salzburg, Austria</nlm:aff></affiliation></author><author><name sortKey="Veauville Merllie, Alice" sort="Veauville Merllie, Alice" uniqKey="Veauville Merllie A" first="Alice" last="Veauville-Merllié">Alice Veauville-Merllié</name><affiliation><nlm:aff id="aff7">Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal, Centre de Biologie et Pathologie Est, Centre Hospitalier Universitaire Lyon, 69500 Bron, France</nlm:aff></affiliation></author><author><name sortKey="Terrile, Caterina" sort="Terrile, Caterina" uniqKey="Terrile C" first="Caterina" last="Terrile">Caterina Terrile</name><affiliation><nlm:aff id="aff3">Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Schwarzmayr, Thomas" sort="Schwarzmayr, Thomas" uniqKey="Schwarzmayr T" first="Thomas" last="Schwarzmayr">Thomas Schwarzmayr</name><affiliation><nlm:aff id="aff2">Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Haack, Tobias B" sort="Haack, Tobias B" uniqKey="Haack T" first="Tobias B." last="Haack">Tobias B. Haack</name><affiliation><nlm:aff id="aff2">Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Auranen, Mari" sort="Auranen, Mari" uniqKey="Auranen M" first="Mari" last="Auranen">Mari Auranen</name><affiliation><nlm:aff id="aff8">Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, 340 Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Leone, Piero" sort="Leone, Piero" uniqKey="Leone P" first="Piero" last="Leone">Piero Leone</name><affiliation><nlm:aff id="aff4">Department of Biosciences, Biotechnology, and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, Italy</nlm:aff></affiliation></author><author><name sortKey="Galluccio, Michele" sort="Galluccio, Michele" uniqKey="Galluccio M" first="Michele" last="Galluccio">Michele Galluccio</name><affiliation><nlm:aff id="aff9">Department DiBEST (Biology, Ecology, and Earth Sciences), University of Calabria, 87036 Arcavacata di Rende, Italy</nlm:aff></affiliation></author><author><name sortKey="Imbard, Apolline" sort="Imbard, Apolline" uniqKey="Imbard A" first="Apolline" last="Imbard">Apolline Imbard</name><affiliation><nlm:aff id="aff10">Biochemistry Hormonology Laboratory, Robert-Debré Hospital, 75019 Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff11">Pharmacy Faculty, Paris Sud University, 92019 Chatenay-Malabry, France</nlm:aff></affiliation></author><author><name sortKey="Gutierrez Rios, Purificacion" sort="Gutierrez Rios, Purificacion" uniqKey="Gutierrez Rios P" first="Purificacion" last="Gutierrez-Rios">Purificacion Gutierrez-Rios</name><affiliation><nlm:aff id="aff5">Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK</nlm:aff></affiliation><affiliation><nlm:aff id="aff12">Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide, 41013 Seville, Spain</nlm:aff></affiliation></author><author><name sortKey="Palmfeldt, Johan" sort="Palmfeldt, Johan" uniqKey="Palmfeldt J" first="Johan" last="Palmfeldt">Johan Palmfeldt</name><affiliation><nlm:aff id="aff1">Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and University Hospital, 8200 Aarhus N, Denmark</nlm:aff></affiliation></author><author><name sortKey="Graf, Elisabeth" sort="Graf, Elisabeth" uniqKey="Graf E" first="Elisabeth" last="Graf">Elisabeth Graf</name><affiliation><nlm:aff id="aff3">Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Vianey Saban, Christine" sort="Vianey Saban, Christine" uniqKey="Vianey Saban C" first="Christine" last="Vianey-Saban">Christine Vianey-Saban</name><affiliation><nlm:aff id="aff7">Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal, Centre de Biologie et Pathologie Est, Centre Hospitalier Universitaire Lyon, 69500 Bron, France</nlm:aff></affiliation></author><author><name sortKey="Oppenheim, Marcus" sort="Oppenheim, Marcus" uniqKey="Oppenheim M" first="Marcus" last="Oppenheim">Marcus Oppenheim</name><affiliation><nlm:aff id="aff13">Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, London WCIN 3BG, UK</nlm:aff></affiliation></author><author><name sortKey="Schiff, Manuel" sort="Schiff, Manuel" uniqKey="Schiff M" first="Manuel" last="Schiff">Manuel Schiff</name><affiliation><nlm:aff id="aff14">INSERM UMR 1141, Hôpital Robert Debré, 75019 Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff15">Reference Center for Inherited Metabolic Diseases, Robert-Debré Hospital, Assistance Publique – Hôpitaux de Paris, 75019 Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff16">Faculté de Médecine Denis Diderot, Université Paris Diderot (Paris 7), 75013 Paris, France</nlm:aff></affiliation></author><author><name sortKey="Pichard, Samia" sort="Pichard, Samia" uniqKey="Pichard S" first="Samia" last="Pichard">Samia Pichard</name><affiliation><nlm:aff id="aff15">Reference Center for Inherited Metabolic Diseases, Robert-Debré Hospital, Assistance Publique – Hôpitaux de Paris, 75019 Paris, France</nlm:aff></affiliation></author><author><name sortKey="Rigal, Odile" sort="Rigal, Odile" uniqKey="Rigal O" first="Odile" last="Rigal">Odile Rigal</name><affiliation><nlm:aff id="aff10">Biochemistry Hormonology Laboratory, Robert-Debré Hospital, 75019 Paris, France</nlm:aff></affiliation></author><author><name sortKey="Pyle, Angela" sort="Pyle, Angela" uniqKey="Pyle A" first="Angela" last="Pyle">Angela Pyle</name><affiliation><nlm:aff id="aff5">Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK</nlm:aff></affiliation></author><author><name sortKey="Chinnery, Patrick F" sort="Chinnery, Patrick F" uniqKey="Chinnery P" first="Patrick F." last="Chinnery">Patrick F. Chinnery</name><affiliation><nlm:aff id="aff5">Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK</nlm:aff></affiliation><affiliation><nlm:aff id="aff17">Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0QQ, UK</nlm:aff></affiliation></author><author><name sortKey="Konstantopoulou, Vassiliki" sort="Konstantopoulou, Vassiliki" uniqKey="Konstantopoulou V" first="Vassiliki" last="Konstantopoulou">Vassiliki Konstantopoulou</name><affiliation><nlm:aff id="aff18">Department of Pediatrics, Medical University of Vienna, 1090 Vienna, Austria</nlm:aff></affiliation></author><author><name sortKey="Moslinger, Dorothea" sort="Moslinger, Dorothea" uniqKey="Moslinger D" first="Dorothea" last="Möslinger">Dorothea Möslinger</name><affiliation><nlm:aff id="aff18">Department of Pediatrics, Medical University of Vienna, 1090 Vienna, Austria</nlm:aff></affiliation></author><author><name sortKey="Feichtinger, Rene G" sort="Feichtinger, Rene G" uniqKey="Feichtinger R" first="René G." last="Feichtinger">René G. Feichtinger</name><affiliation><nlm:aff id="aff6">Department of Paediatrics, Paracelsus Medical University, SALK Salzburg, 5020 Salzburg, Austria</nlm:aff></affiliation></author><author><name sortKey="Talim, Beril" sort="Talim, Beril" uniqKey="Talim B" first="Beril" last="Talim">Beril Talim</name><affiliation><nlm:aff id="aff19">Pathology Unit, Department of Pediatrics, Hacettepe University Children’s Hospital, 06100 Ankara, Turkey</nlm:aff></affiliation></author><author><name sortKey="Topaloglu, Haluk" sort="Topaloglu, Haluk" uniqKey="Topaloglu H" first="Haluk" last="Topaloglu">Haluk Topaloglu</name><affiliation><nlm:aff id="aff20">Neurology Unit, Department of Pediatrics, Hacettepe University Children’s Hospital, 06100 Ankara, Turkey</nlm:aff></affiliation></author><author><name sortKey="Coskun, Turgay" sort="Coskun, Turgay" uniqKey="Coskun T" first="Turgay" last="Coskun">Turgay Coskun</name><affiliation><nlm:aff id="aff21">Metabolism Unit, Department of Pediatrics, Hacettepe University Children’s Hospital, 06100 Ankara, Turkey</nlm:aff></affiliation></author><author><name sortKey="Gucer, Safak" sort="Gucer, Safak" uniqKey="Gucer S" first="Safak" last="Gucer">Safak Gucer</name><affiliation><nlm:aff id="aff19">Pathology Unit, Department of Pediatrics, Hacettepe University Children’s Hospital, 06100 Ankara, Turkey</nlm:aff></affiliation></author><author><name sortKey="Botta, Annalisa" sort="Botta, Annalisa" uniqKey="Botta A" first="Annalisa" last="Botta">Annalisa Botta</name><affiliation><nlm:aff id="aff22">Medical Genetics Section, Department of Biomedicine and Prevention, Tor Vergata University of Rome, 00133 Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Pegoraro, Elena" sort="Pegoraro, Elena" uniqKey="Pegoraro E" first="Elena" last="Pegoraro">Elena Pegoraro</name><affiliation><nlm:aff id="aff23">Neuromuscular Center, Department of Neurosciences, University of Padova, 35129 Padova, Italy</nlm:aff></affiliation></author><author><name sortKey="Malena, Adriana" sort="Malena, Adriana" uniqKey="Malena A" first="Adriana" last="Malena">Adriana Malena</name><affiliation><nlm:aff id="aff23">Neuromuscular Center, Department of Neurosciences, University of Padova, 35129 Padova, Italy</nlm:aff></affiliation></author><author><name sortKey="Vergani, Lodovica" sort="Vergani, Lodovica" uniqKey="Vergani L" first="Lodovica" last="Vergani">Lodovica Vergani</name><affiliation><nlm:aff id="aff23">Neuromuscular Center, Department of Neurosciences, University of Padova, 35129 Padova, Italy</nlm:aff></affiliation></author><author><name sortKey="Mazza, Daniela" sort="Mazza, Daniela" uniqKey="Mazza D" first="Daniela" last="Mazzà">Daniela Mazzà</name><affiliation><nlm:aff id="aff24">Italy Institute of Medical Genetics, Catholic University of Roma, 00168 Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Zollino, Marcella" sort="Zollino, Marcella" uniqKey="Zollino M" first="Marcella" last="Zollino">Marcella Zollino</name><affiliation><nlm:aff id="aff24">Italy Institute of Medical Genetics, Catholic University of Roma, 00168 Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Ghezzi, Daniele" sort="Ghezzi, Daniele" uniqKey="Ghezzi D" first="Daniele" last="Ghezzi">Daniele Ghezzi</name><affiliation><nlm:aff id="aff25">Molecular Neurogenetics Unit, Foundation IRCCS Neurological Institute C. Besta, 20126 Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Acquaviva, Cecile" sort="Acquaviva, Cecile" uniqKey="Acquaviva C" first="Cecile" last="Acquaviva">Cecile Acquaviva</name><affiliation><nlm:aff id="aff7">Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal, Centre de Biologie et Pathologie Est, Centre Hospitalier Universitaire Lyon, 69500 Bron, France</nlm:aff></affiliation></author><author><name sortKey="Tyni, Tiina" sort="Tyni, Tiina" uniqKey="Tyni T" first="Tiina" last="Tyni">Tiina Tyni</name><affiliation><nlm:aff id="aff26">Department of Pediatric Neurology, Hospital for Children and Adolescence, Helsinki University Central Hospital, 280 Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Boneh, Avihu" sort="Boneh, Avihu" uniqKey="Boneh A" first="Avihu" last="Boneh">Avihu Boneh</name><affiliation><nlm:aff id="aff27">Murdoch Childrens Research Institute and University of Melbourne, Melbourne, VIC 3010, Australia</nlm:aff></affiliation></author><author><name sortKey="Meitinger, Thomas" sort="Meitinger, Thomas" uniqKey="Meitinger T" first="Thomas" last="Meitinger">Thomas Meitinger</name><affiliation><nlm:aff id="aff2">Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Strom, Tim M" sort="Strom, Tim M" uniqKey="Strom T" first="Tim M." last="Strom">Tim M. Strom</name><affiliation><nlm:aff id="aff2">Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Gregersen, Niels" sort="Gregersen, Niels" uniqKey="Gregersen N" first="Niels" last="Gregersen">Niels Gregersen</name><affiliation><nlm:aff id="aff1">Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and University Hospital, 8200 Aarhus N, Denmark</nlm:aff></affiliation></author><author><name sortKey="Mayr, Johannes A" sort="Mayr, Johannes A" uniqKey="Mayr J" first="Johannes A." last="Mayr">Johannes A. Mayr</name><affiliation><nlm:aff id="aff6">Department of Paediatrics, Paracelsus Medical University, SALK Salzburg, 5020 Salzburg, Austria</nlm:aff></affiliation></author><author><name sortKey="Horvath, Rita" sort="Horvath, Rita" uniqKey="Horvath R" first="Rita" last="Horvath">Rita Horvath</name><affiliation><nlm:aff id="aff5">Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK</nlm:aff></affiliation></author><author><name sortKey="Barile, Maria" sort="Barile, Maria" uniqKey="Barile M" first="Maria" last="Barile">Maria Barile</name><affiliation><nlm:aff id="aff4">Department of Biosciences, Biotechnology, and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, Italy</nlm:aff></affiliation></author><author><name sortKey="Prokisch, Holger" sort="Prokisch, Holger" uniqKey="Prokisch H" first="Holger" last="Prokisch">Holger Prokisch</name><affiliation><nlm:aff id="aff2">Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27259049</idno><idno type="pmc">4908180</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908180</idno><idno type="RBID">PMC:4908180</idno><idno type="doi">10.1016/j.ajhg.2016.04.006</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">001694</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001694</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency</title><author><name sortKey="Olsen, Rikke K J" sort="Olsen, Rikke K J" uniqKey="Olsen R" first="Rikke K. J." last="Olsen">Rikke K. J. Olsen</name><affiliation><nlm:aff id="aff1">Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and University Hospital, 8200 Aarhus N, Denmark</nlm:aff></affiliation></author><author><name sortKey="Ko A Kova, Eliska" sort="Ko A Kova, Eliska" uniqKey="Ko A Kova E" first="Eliška" last="Ko A Ková">Eliška Ko A Ková</name><affiliation><nlm:aff id="aff2">Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Giancaspero, Teresa A" sort="Giancaspero, Teresa A" uniqKey="Giancaspero T" first="Teresa A." last="Giancaspero">Teresa A. Giancaspero</name><affiliation><nlm:aff id="aff4">Department of Biosciences, Biotechnology, and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, Italy</nlm:aff></affiliation></author><author><name sortKey="Mosegaard, Signe" sort="Mosegaard, Signe" uniqKey="Mosegaard S" first="Signe" last="Mosegaard">Signe Mosegaard</name><affiliation><nlm:aff id="aff1">Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and University Hospital, 8200 Aarhus N, Denmark</nlm:aff></affiliation></author><author><name sortKey="Boczonadi, Veronika" sort="Boczonadi, Veronika" uniqKey="Boczonadi V" first="Veronika" last="Boczonadi">Veronika Boczonadi</name><affiliation><nlm:aff id="aff5">Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK</nlm:aff></affiliation></author><author><name sortKey="Matakovi, Lavinija" sort="Matakovi, Lavinija" uniqKey="Matakovi L" first="Lavinija" last="Matakovi">Lavinija Matakovi</name><affiliation><nlm:aff id="aff6">Department of Paediatrics, Paracelsus Medical University, SALK Salzburg, 5020 Salzburg, Austria</nlm:aff></affiliation></author><author><name sortKey="Veauville Merllie, Alice" sort="Veauville Merllie, Alice" uniqKey="Veauville Merllie A" first="Alice" last="Veauville-Merllié">Alice Veauville-Merllié</name><affiliation><nlm:aff id="aff7">Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal, Centre de Biologie et Pathologie Est, Centre Hospitalier Universitaire Lyon, 69500 Bron, France</nlm:aff></affiliation></author><author><name sortKey="Terrile, Caterina" sort="Terrile, Caterina" uniqKey="Terrile C" first="Caterina" last="Terrile">Caterina Terrile</name><affiliation><nlm:aff id="aff3">Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Schwarzmayr, Thomas" sort="Schwarzmayr, Thomas" uniqKey="Schwarzmayr T" first="Thomas" last="Schwarzmayr">Thomas Schwarzmayr</name><affiliation><nlm:aff id="aff2">Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Haack, Tobias B" sort="Haack, Tobias B" uniqKey="Haack T" first="Tobias B." last="Haack">Tobias B. Haack</name><affiliation><nlm:aff id="aff2">Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Auranen, Mari" sort="Auranen, Mari" uniqKey="Auranen M" first="Mari" last="Auranen">Mari Auranen</name><affiliation><nlm:aff id="aff8">Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, 340 Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Leone, Piero" sort="Leone, Piero" uniqKey="Leone P" first="Piero" last="Leone">Piero Leone</name><affiliation><nlm:aff id="aff4">Department of Biosciences, Biotechnology, and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, Italy</nlm:aff></affiliation></author><author><name sortKey="Galluccio, Michele" sort="Galluccio, Michele" uniqKey="Galluccio M" first="Michele" last="Galluccio">Michele Galluccio</name><affiliation><nlm:aff id="aff9">Department DiBEST (Biology, Ecology, and Earth Sciences), University of Calabria, 87036 Arcavacata di Rende, Italy</nlm:aff></affiliation></author><author><name sortKey="Imbard, Apolline" sort="Imbard, Apolline" uniqKey="Imbard A" first="Apolline" last="Imbard">Apolline Imbard</name><affiliation><nlm:aff id="aff10">Biochemistry Hormonology Laboratory, Robert-Debré Hospital, 75019 Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff11">Pharmacy Faculty, Paris Sud University, 92019 Chatenay-Malabry, France</nlm:aff></affiliation></author><author><name sortKey="Gutierrez Rios, Purificacion" sort="Gutierrez Rios, Purificacion" uniqKey="Gutierrez Rios P" first="Purificacion" last="Gutierrez-Rios">Purificacion Gutierrez-Rios</name><affiliation><nlm:aff id="aff5">Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK</nlm:aff></affiliation><affiliation><nlm:aff id="aff12">Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide, 41013 Seville, Spain</nlm:aff></affiliation></author><author><name sortKey="Palmfeldt, Johan" sort="Palmfeldt, Johan" uniqKey="Palmfeldt J" first="Johan" last="Palmfeldt">Johan Palmfeldt</name><affiliation><nlm:aff id="aff1">Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and University Hospital, 8200 Aarhus N, Denmark</nlm:aff></affiliation></author><author><name sortKey="Graf, Elisabeth" sort="Graf, Elisabeth" uniqKey="Graf E" first="Elisabeth" last="Graf">Elisabeth Graf</name><affiliation><nlm:aff id="aff3">Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Vianey Saban, Christine" sort="Vianey Saban, Christine" uniqKey="Vianey Saban C" first="Christine" last="Vianey-Saban">Christine Vianey-Saban</name><affiliation><nlm:aff id="aff7">Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal, Centre de Biologie et Pathologie Est, Centre Hospitalier Universitaire Lyon, 69500 Bron, France</nlm:aff></affiliation></author><author><name sortKey="Oppenheim, Marcus" sort="Oppenheim, Marcus" uniqKey="Oppenheim M" first="Marcus" last="Oppenheim">Marcus Oppenheim</name><affiliation><nlm:aff id="aff13">Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, London WCIN 3BG, UK</nlm:aff></affiliation></author><author><name sortKey="Schiff, Manuel" sort="Schiff, Manuel" uniqKey="Schiff M" first="Manuel" last="Schiff">Manuel Schiff</name><affiliation><nlm:aff id="aff14">INSERM UMR 1141, Hôpital Robert Debré, 75019 Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff15">Reference Center for Inherited Metabolic Diseases, Robert-Debré Hospital, Assistance Publique – Hôpitaux de Paris, 75019 Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff16">Faculté de Médecine Denis Diderot, Université Paris Diderot (Paris 7), 75013 Paris, France</nlm:aff></affiliation></author><author><name sortKey="Pichard, Samia" sort="Pichard, Samia" uniqKey="Pichard S" first="Samia" last="Pichard">Samia Pichard</name><affiliation><nlm:aff id="aff15">Reference Center for Inherited Metabolic Diseases, Robert-Debré Hospital, Assistance Publique – Hôpitaux de Paris, 75019 Paris, France</nlm:aff></affiliation></author><author><name sortKey="Rigal, Odile" sort="Rigal, Odile" uniqKey="Rigal O" first="Odile" last="Rigal">Odile Rigal</name><affiliation><nlm:aff id="aff10">Biochemistry Hormonology Laboratory, Robert-Debré Hospital, 75019 Paris, France</nlm:aff></affiliation></author><author><name sortKey="Pyle, Angela" sort="Pyle, Angela" uniqKey="Pyle A" first="Angela" last="Pyle">Angela Pyle</name><affiliation><nlm:aff id="aff5">Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK</nlm:aff></affiliation></author><author><name sortKey="Chinnery, Patrick F" sort="Chinnery, Patrick F" uniqKey="Chinnery P" first="Patrick F." last="Chinnery">Patrick F. Chinnery</name><affiliation><nlm:aff id="aff5">Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK</nlm:aff></affiliation><affiliation><nlm:aff id="aff17">Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0QQ, UK</nlm:aff></affiliation></author><author><name sortKey="Konstantopoulou, Vassiliki" sort="Konstantopoulou, Vassiliki" uniqKey="Konstantopoulou V" first="Vassiliki" last="Konstantopoulou">Vassiliki Konstantopoulou</name><affiliation><nlm:aff id="aff18">Department of Pediatrics, Medical University of Vienna, 1090 Vienna, Austria</nlm:aff></affiliation></author><author><name sortKey="Moslinger, Dorothea" sort="Moslinger, Dorothea" uniqKey="Moslinger D" first="Dorothea" last="Möslinger">Dorothea Möslinger</name><affiliation><nlm:aff id="aff18">Department of Pediatrics, Medical University of Vienna, 1090 Vienna, Austria</nlm:aff></affiliation></author><author><name sortKey="Feichtinger, Rene G" sort="Feichtinger, Rene G" uniqKey="Feichtinger R" first="René G." last="Feichtinger">René G. Feichtinger</name><affiliation><nlm:aff id="aff6">Department of Paediatrics, Paracelsus Medical University, SALK Salzburg, 5020 Salzburg, Austria</nlm:aff></affiliation></author><author><name sortKey="Talim, Beril" sort="Talim, Beril" uniqKey="Talim B" first="Beril" last="Talim">Beril Talim</name><affiliation><nlm:aff id="aff19">Pathology Unit, Department of Pediatrics, Hacettepe University Children’s Hospital, 06100 Ankara, Turkey</nlm:aff></affiliation></author><author><name sortKey="Topaloglu, Haluk" sort="Topaloglu, Haluk" uniqKey="Topaloglu H" first="Haluk" last="Topaloglu">Haluk Topaloglu</name><affiliation><nlm:aff id="aff20">Neurology Unit, Department of Pediatrics, Hacettepe University Children’s Hospital, 06100 Ankara, Turkey</nlm:aff></affiliation></author><author><name sortKey="Coskun, Turgay" sort="Coskun, Turgay" uniqKey="Coskun T" first="Turgay" last="Coskun">Turgay Coskun</name><affiliation><nlm:aff id="aff21">Metabolism Unit, Department of Pediatrics, Hacettepe University Children’s Hospital, 06100 Ankara, Turkey</nlm:aff></affiliation></author><author><name sortKey="Gucer, Safak" sort="Gucer, Safak" uniqKey="Gucer S" first="Safak" last="Gucer">Safak Gucer</name><affiliation><nlm:aff id="aff19">Pathology Unit, Department of Pediatrics, Hacettepe University Children’s Hospital, 06100 Ankara, Turkey</nlm:aff></affiliation></author><author><name sortKey="Botta, Annalisa" sort="Botta, Annalisa" uniqKey="Botta A" first="Annalisa" last="Botta">Annalisa Botta</name><affiliation><nlm:aff id="aff22">Medical Genetics Section, Department of Biomedicine and Prevention, Tor Vergata University of Rome, 00133 Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Pegoraro, Elena" sort="Pegoraro, Elena" uniqKey="Pegoraro E" first="Elena" last="Pegoraro">Elena Pegoraro</name><affiliation><nlm:aff id="aff23">Neuromuscular Center, Department of Neurosciences, University of Padova, 35129 Padova, Italy</nlm:aff></affiliation></author><author><name sortKey="Malena, Adriana" sort="Malena, Adriana" uniqKey="Malena A" first="Adriana" last="Malena">Adriana Malena</name><affiliation><nlm:aff id="aff23">Neuromuscular Center, Department of Neurosciences, University of Padova, 35129 Padova, Italy</nlm:aff></affiliation></author><author><name sortKey="Vergani, Lodovica" sort="Vergani, Lodovica" uniqKey="Vergani L" first="Lodovica" last="Vergani">Lodovica Vergani</name><affiliation><nlm:aff id="aff23">Neuromuscular Center, Department of Neurosciences, University of Padova, 35129 Padova, Italy</nlm:aff></affiliation></author><author><name sortKey="Mazza, Daniela" sort="Mazza, Daniela" uniqKey="Mazza D" first="Daniela" last="Mazzà">Daniela Mazzà</name><affiliation><nlm:aff id="aff24">Italy Institute of Medical Genetics, Catholic University of Roma, 00168 Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Zollino, Marcella" sort="Zollino, Marcella" uniqKey="Zollino M" first="Marcella" last="Zollino">Marcella Zollino</name><affiliation><nlm:aff id="aff24">Italy Institute of Medical Genetics, Catholic University of Roma, 00168 Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Ghezzi, Daniele" sort="Ghezzi, Daniele" uniqKey="Ghezzi D" first="Daniele" last="Ghezzi">Daniele Ghezzi</name><affiliation><nlm:aff id="aff25">Molecular Neurogenetics Unit, Foundation IRCCS Neurological Institute C. Besta, 20126 Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Acquaviva, Cecile" sort="Acquaviva, Cecile" uniqKey="Acquaviva C" first="Cecile" last="Acquaviva">Cecile Acquaviva</name><affiliation><nlm:aff id="aff7">Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal, Centre de Biologie et Pathologie Est, Centre Hospitalier Universitaire Lyon, 69500 Bron, France</nlm:aff></affiliation></author><author><name sortKey="Tyni, Tiina" sort="Tyni, Tiina" uniqKey="Tyni T" first="Tiina" last="Tyni">Tiina Tyni</name><affiliation><nlm:aff id="aff26">Department of Pediatric Neurology, Hospital for Children and Adolescence, Helsinki University Central Hospital, 280 Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Boneh, Avihu" sort="Boneh, Avihu" uniqKey="Boneh A" first="Avihu" last="Boneh">Avihu Boneh</name><affiliation><nlm:aff id="aff27">Murdoch Childrens Research Institute and University of Melbourne, Melbourne, VIC 3010, Australia</nlm:aff></affiliation></author><author><name sortKey="Meitinger, Thomas" sort="Meitinger, Thomas" uniqKey="Meitinger T" first="Thomas" last="Meitinger">Thomas Meitinger</name><affiliation><nlm:aff id="aff2">Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Strom, Tim M" sort="Strom, Tim M" uniqKey="Strom T" first="Tim M." last="Strom">Tim M. Strom</name><affiliation><nlm:aff id="aff2">Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Gregersen, Niels" sort="Gregersen, Niels" uniqKey="Gregersen N" first="Niels" last="Gregersen">Niels Gregersen</name><affiliation><nlm:aff id="aff1">Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and University Hospital, 8200 Aarhus N, Denmark</nlm:aff></affiliation></author><author><name sortKey="Mayr, Johannes A" sort="Mayr, Johannes A" uniqKey="Mayr J" first="Johannes A." last="Mayr">Johannes A. Mayr</name><affiliation><nlm:aff id="aff6">Department of Paediatrics, Paracelsus Medical University, SALK Salzburg, 5020 Salzburg, Austria</nlm:aff></affiliation></author><author><name sortKey="Horvath, Rita" sort="Horvath, Rita" uniqKey="Horvath R" first="Rita" last="Horvath">Rita Horvath</name><affiliation><nlm:aff id="aff5">Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK</nlm:aff></affiliation></author><author><name sortKey="Barile, Maria" sort="Barile, Maria" uniqKey="Barile M" first="Maria" last="Barile">Maria Barile</name><affiliation><nlm:aff id="aff4">Department of Biosciences, Biotechnology, and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, Italy</nlm:aff></affiliation></author><author><name sortKey="Prokisch, Holger" sort="Prokisch, Holger" uniqKey="Prokisch H" first="Holger" last="Prokisch">Holger Prokisch</name><affiliation><nlm:aff id="aff2">Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany</nlm:aff></affiliation></author></analytic><series><title level="j">American Journal of Human Genetics</title><idno type="ISSN">0002-9297</idno><idno type="eISSN">1537-6605</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Multiple acyl-CoA dehydrogenase deficiencies (MADDs) are a heterogeneous group of metabolic disorders with combined respiratory-chain deficiency and a neuromuscular phenotype. Despite recent advances in understanding the genetic basis of MADD, a number of cases remain unexplained. Here, we report clinically relevant variants in <italic>FLAD1</italic>, which encodes FAD synthase (FADS), as the cause of MADD and respiratory-chain dysfunction in nine individuals recruited from metabolic centers in six countries. In most individuals, we identified biallelic frameshift variants in the molybdopterin binding (MPTb) domain, located upstream of the FADS domain. Inasmuch as FADS is essential for cellular supply of FAD cofactors, the finding of biallelic frameshift variants was unexpected. Using RNA sequencing analysis combined with protein mass spectrometry, we discovered <italic>FLAD1</italic> isoforms, which only encode the FADS domain. The existence of these isoforms might explain why affected individuals with biallelic <italic>FLAD1</italic> frameshift variants still harbor substantial FADS activity. Another group of individuals with a milder phenotype responsive to riboflavin were shown to have single amino acid changes in the FADS domain. When produced in <italic>E. coli,</italic> these mutant FADS proteins resulted in impaired but detectable FADS activity; for one of the variant proteins, the addition of FAD significantly improved protein stability, arguing for a chaperone-like action similar to what has been reported in other riboflavin-responsive inborn errors of metabolism. In conclusion, our studies identify <italic>FLAD1</italic> variants as a cause of potentially treatable inborn errors of metabolism manifesting with MADD and shed light on the mechanisms by which FADS ensures cellular FAD homeostasis.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Hum Genet</journal-id><journal-id journal-id-type="iso-abbrev">Am. J. Hum. Genet</journal-id><journal-title-group><journal-title>American Journal of Human Genetics</journal-title></journal-title-group><issn pub-type="ppub">0002-9297</issn><issn pub-type="epub">1537-6605</issn><publisher><publisher-name>Elsevier</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27259049</article-id><article-id pub-id-type="pmc">4908180</article-id><article-id pub-id-type="publisher-id">S0002-9297(16)30101-X</article-id><article-id pub-id-type="doi">10.1016/j.ajhg.2016.04.006</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Olsen</surname><given-names>Rikke K.J.</given-names></name><email>rikke.olsen@clin.au.dk</email><xref rid="aff1" ref-type="aff">1</xref><xref rid="fn1" ref-type="fn">28</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib><contrib contrib-type="author"><name><surname>Koňaříková</surname><given-names>Eliška</given-names></name><xref rid="aff2" ref-type="aff">2</xref><xref rid="aff3" ref-type="aff">3</xref><xref rid="fn1" ref-type="fn">28</xref></contrib><contrib contrib-type="author"><name><surname>Giancaspero</surname><given-names>Teresa A.</given-names></name><xref rid="aff4" ref-type="aff">4</xref><xref rid="fn1" ref-type="fn">28</xref></contrib><contrib contrib-type="author"><name><surname>Mosegaard</surname><given-names>Signe</given-names></name><xref rid="aff1" ref-type="aff">1</xref><xref rid="fn1" ref-type="fn">28</xref></contrib><contrib contrib-type="author"><name><surname>Boczonadi</surname><given-names>Veronika</given-names></name><xref rid="aff5" ref-type="aff">5</xref><xref rid="fn1" ref-type="fn">28</xref></contrib><contrib contrib-type="author"><name><surname>Mataković</surname><given-names>Lavinija</given-names></name><xref rid="aff6" ref-type="aff">6</xref><xref rid="fn1" ref-type="fn">28</xref></contrib><contrib contrib-type="author"><name><surname>Veauville-Merllié</surname><given-names>Alice</given-names></name><xref rid="aff7" ref-type="aff">7</xref></contrib><contrib contrib-type="author"><name><surname>Terrile</surname><given-names>Caterina</given-names></name><xref rid="aff3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Schwarzmayr</surname><given-names>Thomas</given-names></name><xref rid="aff2" ref-type="aff">2</xref><xref rid="aff3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Haack</surname><given-names>Tobias B.</given-names></name><xref rid="aff2" ref-type="aff">2</xref><xref rid="aff3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Auranen</surname><given-names>Mari</given-names></name><xref rid="aff8" ref-type="aff">8</xref></contrib><contrib contrib-type="author"><name><surname>Leone</surname><given-names>Piero</given-names></name><xref rid="aff4" ref-type="aff">4</xref></contrib><contrib contrib-type="author"><name><surname>Galluccio</surname><given-names>Michele</given-names></name><xref rid="aff9" ref-type="aff">9</xref></contrib><contrib contrib-type="author"><name><surname>Imbard</surname><given-names>Apolline</given-names></name><xref rid="aff10" ref-type="aff">10</xref><xref rid="aff11" ref-type="aff">11</xref></contrib><contrib contrib-type="author"><name><surname>Gutierrez-Rios</surname><given-names>Purificacion</given-names></name><xref rid="aff5" ref-type="aff">5</xref><xref rid="aff12" ref-type="aff">12</xref></contrib><contrib contrib-type="author"><name><surname>Palmfeldt</surname><given-names>Johan</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Graf</surname><given-names>Elisabeth</given-names></name><xref rid="aff3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Vianey-Saban</surname><given-names>Christine</given-names></name><xref rid="aff7" ref-type="aff">7</xref></contrib><contrib contrib-type="author"><name><surname>Oppenheim</surname><given-names>Marcus</given-names></name><xref rid="aff13" ref-type="aff">13</xref></contrib><contrib contrib-type="author"><name><surname>Schiff</surname><given-names>Manuel</given-names></name><xref rid="aff14" ref-type="aff">14</xref><xref rid="aff15" ref-type="aff">15</xref><xref rid="aff16" ref-type="aff">16</xref></contrib><contrib contrib-type="author"><name><surname>Pichard</surname><given-names>Samia</given-names></name><xref rid="aff15" ref-type="aff">15</xref></contrib><contrib contrib-type="author"><name><surname>Rigal</surname><given-names>Odile</given-names></name><xref rid="aff10" ref-type="aff">10</xref></contrib><contrib contrib-type="author"><name><surname>Pyle</surname><given-names>Angela</given-names></name><xref rid="aff5" ref-type="aff">5</xref></contrib><contrib contrib-type="author"><name><surname>Chinnery</surname><given-names>Patrick F.</given-names></name><xref rid="aff5" ref-type="aff">5</xref><xref rid="aff17" ref-type="aff">17</xref></contrib><contrib contrib-type="author"><name><surname>Konstantopoulou</surname><given-names>Vassiliki</given-names></name><xref rid="aff18" ref-type="aff">18</xref></contrib><contrib contrib-type="author"><name><surname>Möslinger</surname><given-names>Dorothea</given-names></name><xref rid="aff18" ref-type="aff">18</xref></contrib><contrib contrib-type="author"><name><surname>Feichtinger</surname><given-names>René G.</given-names></name><xref rid="aff6" ref-type="aff">6</xref></contrib><contrib contrib-type="author"><name><surname>Talim</surname><given-names>Beril</given-names></name><xref rid="aff19" ref-type="aff">19</xref></contrib><contrib contrib-type="author"><name><surname>Topaloglu</surname><given-names>Haluk</given-names></name><xref rid="aff20" ref-type="aff">20</xref></contrib><contrib contrib-type="author"><name><surname>Coskun</surname><given-names>Turgay</given-names></name><xref rid="aff21" ref-type="aff">21</xref></contrib><contrib contrib-type="author"><name><surname>Gucer</surname><given-names>Safak</given-names></name><xref rid="aff19" ref-type="aff">19</xref></contrib><contrib contrib-type="author"><name><surname>Botta</surname><given-names>Annalisa</given-names></name><xref rid="aff22" ref-type="aff">22</xref></contrib><contrib contrib-type="author"><name><surname>Pegoraro</surname><given-names>Elena</given-names></name><xref rid="aff23" ref-type="aff">23</xref></contrib><contrib contrib-type="author"><name><surname>Malena</surname><given-names>Adriana</given-names></name><xref rid="aff23" ref-type="aff">23</xref></contrib><contrib contrib-type="author"><name><surname>Vergani</surname><given-names>Lodovica</given-names></name><xref rid="aff23" ref-type="aff">23</xref></contrib><contrib contrib-type="author"><name><surname>Mazzà</surname><given-names>Daniela</given-names></name><xref rid="aff24" ref-type="aff">24</xref></contrib><contrib contrib-type="author"><name><surname>Zollino</surname><given-names>Marcella</given-names></name><xref rid="aff24" ref-type="aff">24</xref></contrib><contrib contrib-type="author"><name><surname>Ghezzi</surname><given-names>Daniele</given-names></name><xref rid="aff25" ref-type="aff">25</xref></contrib><contrib contrib-type="author"><name><surname>Acquaviva</surname><given-names>Cecile</given-names></name><xref rid="aff7" ref-type="aff">7</xref></contrib><contrib contrib-type="author"><name><surname>Tyni</surname><given-names>Tiina</given-names></name><xref rid="aff26" ref-type="aff">26</xref></contrib><contrib contrib-type="author"><name><surname>Boneh</surname><given-names>Avihu</given-names></name><xref rid="aff27" ref-type="aff">27</xref></contrib><contrib contrib-type="author"><name><surname>Meitinger</surname><given-names>Thomas</given-names></name><xref rid="aff2" ref-type="aff">2</xref><xref rid="aff3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Strom</surname><given-names>Tim M.</given-names></name><xref rid="aff2" ref-type="aff">2</xref><xref rid="aff3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Gregersen</surname><given-names>Niels</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Mayr</surname><given-names>Johannes A.</given-names></name><xref rid="aff6" ref-type="aff">6</xref><xref rid="fn2" ref-type="fn">29</xref></contrib><contrib contrib-type="author"><name><surname>Horvath</surname><given-names>Rita</given-names></name><xref rid="aff5" ref-type="aff">5</xref><xref rid="fn2" ref-type="fn">29</xref></contrib><contrib contrib-type="author"><name><surname>Barile</surname><given-names>Maria</given-names></name><email>maria.barile@uniba.it</email><xref rid="aff4" ref-type="aff">4</xref><xref rid="fn2" ref-type="fn">29</xref><xref rid="cor2" ref-type="corresp">∗∗</xref></contrib><contrib contrib-type="author"><name><surname>Prokisch</surname><given-names>Holger</given-names></name><xref rid="aff2" ref-type="aff">2</xref><xref rid="aff3" ref-type="aff">3</xref><xref rid="fn2" ref-type="fn">29</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and University Hospital, 8200 Aarhus N, Denmark</aff><aff id="aff2"><label>2</label>Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany</aff><aff id="aff3"><label>3</label>Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany</aff><aff id="aff4"><label>4</label>Department of Biosciences, Biotechnology, and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, Italy</aff><aff id="aff5"><label>5</label>Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK</aff><aff id="aff6"><label>6</label>Department of Paediatrics, Paracelsus Medical University, SALK Salzburg, 5020 Salzburg, Austria</aff><aff id="aff7"><label>7</label>Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal, Centre de Biologie et Pathologie Est, Centre Hospitalier Universitaire Lyon, 69500 Bron, France</aff><aff id="aff8"><label>8</label>Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, 340 Helsinki, Finland</aff><aff id="aff9"><label>9</label>Department DiBEST (Biology, Ecology, and Earth Sciences), University of Calabria, 87036 Arcavacata di Rende, Italy</aff><aff id="aff10"><label>10</label>Biochemistry Hormonology Laboratory, Robert-Debré Hospital, 75019 Paris, France</aff><aff id="aff11"><label>11</label>Pharmacy Faculty, Paris Sud University, 92019 Chatenay-Malabry, France</aff><aff id="aff12"><label>12</label>Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide, 41013 Seville, Spain</aff><aff id="aff13"><label>13</label>Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, London WCIN 3BG, UK</aff><aff id="aff14"><label>14</label>INSERM UMR 1141, Hôpital Robert Debré, 75019 Paris, France</aff><aff id="aff15"><label>15</label>Reference Center for Inherited Metabolic Diseases, Robert-Debré Hospital, Assistance Publique – Hôpitaux de Paris, 75019 Paris, France</aff><aff id="aff16"><label>16</label>Faculté de Médecine Denis Diderot, Université Paris Diderot (Paris 7), 75013 Paris, France</aff><aff id="aff17"><label>17</label>Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0QQ, UK</aff><aff id="aff18"><label>18</label>Department of Pediatrics, Medical University of Vienna, 1090 Vienna, Austria</aff><aff id="aff19"><label>19</label>Pathology Unit, Department of Pediatrics, Hacettepe University Children’s Hospital, 06100 Ankara, Turkey</aff><aff id="aff20"><label>20</label>Neurology Unit, Department of Pediatrics, Hacettepe University Children’s Hospital, 06100 Ankara, Turkey</aff><aff id="aff21"><label>21</label>Metabolism Unit, Department of Pediatrics, Hacettepe University Children’s Hospital, 06100 Ankara, Turkey</aff><aff id="aff22"><label>22</label>Medical Genetics Section, Department of Biomedicine and Prevention, Tor Vergata University of Rome, 00133 Rome, Italy</aff><aff id="aff23"><label>23</label>Neuromuscular Center, Department of Neurosciences, University of Padova, 35129 Padova, Italy</aff><aff id="aff24"><label>24</label>Italy Institute of Medical Genetics, Catholic University of Roma, 00168 Rome, Italy</aff><aff id="aff25"><label>25</label>Molecular Neurogenetics Unit, Foundation IRCCS Neurological Institute C. Besta, 20126 Milan, Italy</aff><aff id="aff26"><label>26</label>Department of Pediatric Neurology, Hospital for Children and Adolescence, Helsinki University Central Hospital, 280 Helsinki, Finland</aff><aff id="aff27"><label>27</label>Murdoch Childrens Research Institute and University of Melbourne, Melbourne, VIC 3010, Australia</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author <email>rikke.olsen@clin.au.dk</email></corresp><corresp id="cor2"><label>∗∗</label>Corresponding author <email>maria.barile@uniba.it</email></corresp><fn id="fn1"><label>28</label><p id="ntpara0010">These authors contributed equally to this work</p></fn><fn id="fn2"><label>29</label><p id="ntpara0015">These authors contributed equally to this work</p></fn></author-notes><pub-date pub-type="ppub"><day>02</day><month>6</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>02</day><month>6</month><year>2016</year></pub-date><volume>98</volume><issue>6</issue><fpage>1130</fpage><lpage>1145</lpage><history><date date-type="received"><day>22</day><month>1</month><year>2016</year></date><date date-type="accepted"><day>13</day><month>4</month><year>2016</year></date></history><permissions><copyright-statement>© 2016 The Authors</copyright-statement><copyright-year>2016</copyright-year><license license-type="CC BY-NC-ND" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/"><license-p>This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).</license-p></license></permissions><abstract id="abs0010"><p>Multiple acyl-CoA dehydrogenase deficiencies (MADDs) are a heterogeneous group of metabolic disorders with combined respiratory-chain deficiency and a neuromuscular phenotype. Despite recent advances in understanding the genetic basis of MADD, a number of cases remain unexplained. Here, we report clinically relevant variants in <italic>FLAD1</italic>, which encodes FAD synthase (FADS), as the cause of MADD and respiratory-chain dysfunction in nine individuals recruited from metabolic centers in six countries. In most individuals, we identified biallelic frameshift variants in the molybdopterin binding (MPTb) domain, located upstream of the FADS domain. Inasmuch as FADS is essential for cellular supply of FAD cofactors, the finding of biallelic frameshift variants was unexpected. Using RNA sequencing analysis combined with protein mass spectrometry, we discovered <italic>FLAD1</italic> isoforms, which only encode the FADS domain. The existence of these isoforms might explain why affected individuals with biallelic <italic>FLAD1</italic> frameshift variants still harbor substantial FADS activity. Another group of individuals with a milder phenotype responsive to riboflavin were shown to have single amino acid changes in the FADS domain. When produced in <italic>E. coli,</italic> these mutant FADS proteins resulted in impaired but detectable FADS activity; for one of the variant proteins, the addition of FAD significantly improved protein stability, arguing for a chaperone-like action similar to what has been reported in other riboflavin-responsive inborn errors of metabolism. In conclusion, our studies identify <italic>FLAD1</italic> variants as a cause of potentially treatable inborn errors of metabolism manifesting with MADD and shed light on the mechanisms by which FADS ensures cellular FAD homeostasis.</p></abstract></article-meta><notes><p id="misc0010">Published: June 2, 2016</p></notes></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001694 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 001694 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.33. |  |