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Gain-of-function mutations in KCNK3 cause a developmental disorder with sleep apnea.
Sörmann, Janina; Schewe, Marcus; Proks, Peter; Jouen-Tachoire, Thibault; Rao, Shanlin; Riel, Elena B; Agre, Katherine E; Begtrup, Amber; Dean, John; Descartes, Maria; Fischer, Jan; Gardham, Alice; Lahner, Carrie; Mark, Paul R; Muppidi, Srikanth; Pichurin, Pavel N; Porrmann, Joseph; Schallner, Jens; Smith, Kirstin; Straub, Volker; Vasudevan, Pradeep; Willaert, Rebecca; Carpenter, Elisabeth P; Rödström, Karin E J; Hahn, Michael G; Müller, Thomas; Baukrowitz, Thomas; Hurles, Matthew E; Wright, Caroline F; Tucker, Stephen J.
Afiliación
  • Sörmann J; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford, UK.
  • Schewe M; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK.
  • Proks P; Institute of Physiology, Faculty of Medicine, Kiel University, Kiel, Germany.
  • Jouen-Tachoire T; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford, UK.
  • Rao S; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK.
  • Riel EB; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford, UK.
  • Agre KE; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK.
  • Begtrup A; Department of Pharmacology, University of Oxford, Oxford, UK.
  • Dean J; OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford, UK.
  • Descartes M; Department of Biochemistry, University of Oxford, Oxford, UK.
  • Fischer J; Institute of Physiology, Faculty of Medicine, Kiel University, Kiel, Germany.
  • Gardham A; Mayo Clinic, Rochester, MN, USA.
  • Lahner C; GeneDx, Gaithersburg, MD, USA.
  • Mark PR; Department of Medical Genetics, NHS Grampian, Aberdeen, UK.
  • Muppidi S; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Pichurin PN; Institute for Clinical Genetics, Universitätsklinikum, Technischen Universität Dresden, Dresden, Germany.
  • Porrmann J; North West Thames Regional Genetics Service, London North West Healthcare NHS Trust, London, UK.
  • Schallner J; Mayo Clinic, Rochester, MN, USA.
  • Smith K; Spectrum Health Medical Genetics, Grand Rapids, MI, USA.
  • Straub V; Stanford Neurosciences Health Center, Palo Alto, CA, USA.
  • Vasudevan P; Mayo Clinic, Rochester, MN, USA.
  • Willaert R; Institute for Clinical Genetics, Universitätsklinikum, Technischen Universität Dresden, Dresden, Germany.
  • Carpenter EP; Department of Neuropediatrics, Universitätsklinikum, Technischen Universität Dresden, Dresden, Germany.
  • Rödström KEJ; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Hahn MG; Institute of Translational and Clinical Research, Newcastle University, Newcastle upon Tyne, UK.
  • Müller T; University Hospitals of Leicester NHS Trust, Leicester Royal Infirmary, Leicester, UK.
  • Baukrowitz T; GeneDx, Gaithersburg, MD, USA.
  • Hurles ME; OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford, UK.
  • Wright CF; Centre for Medicines Discovery, University of Oxford, Oxford, UK.
  • Tucker SJ; Centre for Medicines Discovery, University of Oxford, Oxford, UK.
Nat Genet ; 54(10): 1534-1543, 2022 Oct.
Article en En | MEDLINE | ID: mdl-36195757
Sleep apnea is a common disorder that represents a global public health burden. KCNK3 encodes TASK-1, a K+ channel implicated in the control of breathing, but its link with sleep apnea remains poorly understood. Here we describe a new developmental disorder with associated sleep apnea (developmental delay with sleep apnea, or DDSA) caused by rare de novo gain-of-function mutations in KCNK3. The mutations cluster around the 'X-gate', a gating motif that controls channel opening, and produce overactive channels that no longer respond to inhibition by G-protein-coupled receptor pathways. However, despite their defective X-gating, these mutant channels can still be inhibited by a range of known TASK channel inhibitors. These results not only highlight an important new role for TASK-1 K+ channels and their link with sleep apnea but also identify possible therapeutic strategies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes de la Apnea del Sueño / Mutación con Ganancia de Función Límite: Child / Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes de la Apnea del Sueño / Mutación con Ganancia de Función Límite: Child / Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos