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Biallelic Mutations in ATP5F1D, which Encodes a Subunit of ATP Synthase, Cause a Metabolic Disorder.
Oláhová, Monika; Yoon, Wan Hee; Thompson, Kyle; Jangam, Sharayu; Fernandez, Liliana; Davidson, Jean M; Kyle, Jennifer E; Grove, Megan E; Fisk, Dianna G; Kohler, Jennefer N; Holmes, Matthew; Dries, Annika M; Huang, Yong; Zhao, Chunli; Contrepois, Kévin; Zappala, Zachary; Frésard, Laure; Waggott, Daryl; Zink, Erika M; Kim, Young-Mo; Heyman, Heino M; Stratton, Kelly G; Webb-Robertson, Bobbie-Jo M; Snyder, Michael; Merker, Jason D; Montgomery, Stephen B; Fisher, Paul G; Feichtinger, René G; Mayr, Johannes A; Hall, Julie; Barbosa, Ines A; Simpson, Michael A; Deshpande, Charu; Waters, Katrina M; Koeller, David M; Metz, Thomas O; Morris, Andrew A; Schelley, Susan; Cowan, Tina; Friederich, Marisa W; McFarland, Robert; Van Hove, Johan L K; Enns, Gregory M; Yamamoto, Shinya; Ashley, Euan A; Wangler, Michael F; Taylor, Robert W; Bellen, Hugo J; Bernstein, Jonathan A; Wheeler, Matthew T.
Afiliação
  • Oláhová M; Wellcome Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Yoon WH; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Thompson K; Wellcome Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Jangam S; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Fernandez L; Center for Undiagnosed Diseases, Stanford University, Stanford, CA 94305, USA.
  • Davidson JM; Center for Undiagnosed Diseases, Stanford University, Stanford, CA 94305, USA.
  • Kyle JE; Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Grove ME; Clinical Genomics Program, Stanford Health Care, Stanford, CA 94305, USA.
  • Fisk DG; Clinical Genomics Program, Stanford Health Care, Stanford, CA 94305, USA.
  • Kohler JN; Center for Undiagnosed Diseases, Stanford University, Stanford, CA 94305, USA.
  • Holmes M; Wellcome Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Dries AM; Center for Undiagnosed Diseases, Stanford University, Stanford, CA 94305, USA.
  • Huang Y; Center for Undiagnosed Diseases, Stanford University, Stanford, CA 94305, USA.
  • Zhao C; Center for Undiagnosed Diseases, Stanford University, Stanford, CA 94305, USA.
  • Contrepois K; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Zappala Z; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Frésard L; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Waggott D; Center for Undiagnosed Diseases, Stanford University, Stanford, CA 94305, USA.
  • Zink EM; Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Kim YM; Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Heyman HM; Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Stratton KG; Computing & Analytics Division, National Security Directorate, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Webb-Robertson BM; Computing & Analytics Division, National Security Directorate, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Snyder M; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Merker JD; Clinical Genomics Program, Stanford Health Care, Stanford, CA 94305, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Montgomery SB; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Fisher PG; Center for Undiagnosed Diseases, Stanford University, Stanford, CA 94305, USA.
  • Feichtinger RG; Department of Pediatrics, Paracelsus Medical University, 5020 Salzburg, Austria.
  • Mayr JA; Department of Pediatrics, Paracelsus Medical University, 5020 Salzburg, Austria.
  • Hall J; Department of Neuroradiology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK.
  • Barbosa IA; Department of Medical and Molecular Genetics, King's College London School of Basic and Medical Biosciences, London SE1 9RT, UK.
  • Simpson MA; Department of Medical and Molecular Genetics, King's College London School of Basic and Medical Biosciences, London SE1 9RT, UK.
  • Deshpande C; Clinical Genetics Unit, Guys and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK.
  • Waters KM; Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Koeller DM; Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR 97239, USA.
  • Metz TO; Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Morris AA; Institute of Human Development, University of Manchester, Manchester M13 9PL, UK; Willink Metabolic Unit, Genomic Medicine, Saint Mary's Hospital, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK.
  • Schelley S; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Cowan T; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Friederich MW; Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado at Denver, Aurora, CO 80045, USA.
  • McFarland R; Wellcome Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Van Hove JLK; Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado at Denver, Aurora, CO 80045, USA.
  • Enns GM; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Yamamoto S; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Department of Neuro
  • Ashley EA; Center for Undiagnosed Diseases, Stanford University, Stanford, CA 94305, USA; Clinical Genomics Program, Stanford Health Care, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Stanford University School of Medi
  • Wangler MF; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.
  • Taylor RW; Wellcome Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Bellen HJ; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Duncan Neurological Resea
  • Bernstein JA; Center for Undiagnosed Diseases, Stanford University, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Wheeler MT; Center for Undiagnosed Diseases, Stanford University, Stanford, CA 94305, USA; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: wheelerm@stanford.edu.
Am J Hum Genet ; 102(3): 494-504, 2018 03 01.
Article em En | MEDLINE | ID: mdl-29478781
ABSTRACT
ATP synthase, H+ transporting, mitochondrial F1 complex, δ subunit (ATP5F1D; formerly ATP5D) is a subunit of mitochondrial ATP synthase and plays an important role in coupling proton translocation and ATP production. Here, we describe two individuals, each with homozygous missense variants in ATP5F1D, who presented with episodic lethargy, metabolic acidosis, 3-methylglutaconic aciduria, and hyperammonemia. Subject 1, homozygous for c.245C>T (p.Pro82Leu), presented with recurrent metabolic decompensation starting in the neonatal period, and subject 2, homozygous for c.317T>G (p.Val106Gly), presented with acute encephalopathy in childhood. Cultured skin fibroblasts from these individuals exhibited impaired assembly of F1FO ATP synthase and subsequent reduced complex V activity. Cells from subject 1 also exhibited a significant decrease in mitochondrial cristae. Knockdown of Drosophila ATPsynδ, the ATP5F1D homolog, in developing eyes and brains caused a near complete loss of the fly head, a phenotype that was fully rescued by wild-type human ATP5F1D. In contrast, expression of the ATP5F1D c.245C>T and c.317T>G variants rescued the head-size phenotype but recapitulated the eye and antennae defects seen in other genetic models of mitochondrial oxidative phosphorylation deficiency. Our data establish c.245C>T (p.Pro82Leu) and c.317T>G (p.Val106Gly) in ATP5F1D as pathogenic variants leading to a Mendelian mitochondrial disease featuring episodic metabolic decompensation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Subunidades Proteicas / ATPases Mitocondriais Próton-Translocadoras / Alelos / Doenças Metabólicas / Mutação Tipo de estudo: Prognostic_studies Limite: Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Revista: Am J Hum Genet Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Reino Unido
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Subunidades Proteicas / ATPases Mitocondriais Próton-Translocadoras / Alelos / Doenças Metabólicas / Mutação Tipo de estudo: Prognostic_studies Limite: Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Revista: Am J Hum Genet Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Reino Unido