2. Academic Validation
  3. Transcriptional regulator PRDM12 is essential for human pain perception

Transcriptional regulator PRDM12 is essential for human pain perception

  • Nat Genet. 2015 Jul;47(7):803-8. doi: 10.1038/ng.3308.
Ya-Chun Chen 1,  Michaela Auer-Grumbach 2,  Shinya Matsukawa 3,  Manuela Zitzelsberger 4,  Andreas C Themistocleous 5,  Tim M Strom 6,  Chrysanthi Samara 7,  Adrian W Moore 8,  Lily Ting-Yin Cho 9,  Gareth T Young 9,  Caecilia Weiss 4,  Maria Schabhüttl 2,  Rolf Stucka 4,  Annina B Schmid 10,  Yesim Parman 11,  Luitgard Graul-Neumann 12,  Wolfram Heinritz 13,  Eberhard Passarge 14,  Rosemarie M Watson 15,  Jens Michael Hertz 16,  Ute Moog 17,  Manuela Baumgartner 18,  Enza Maria Valente 19,  Diego Pereira 20,  Carlos M Restrepo 21,  Istvan Katona 22,  Marina Dusl 4,  Claudia Stendel 23,  Thomas Wieland 24,  Fay Stafford 1,  Frank Reimann 25,  Katja von Au 26,  Christian Finke 27,  Patrick J Willems 28,  Michael S Nahorski 1,  Samiha S Shaikh 1,  Ofélia P Carvalho 1,  Adeline K Nicholas 29,  Gulshan Karbani 30,  Maeve A McAleer 15,  Maria Roberta Cilio 31,  John C McHugh 32,  Sinead M Murphy 33,  Alan D Irvine 34,  Uffe Birk Jensen 35,  Reinhard Windhager 2,  Joachim Weis 22,  Carsten Bergmann 36,  Bernd Rautenstrauss 37,  Jonathan Baets 38,  Peter De Jonghe 38,  Mary M Reilly 39,  Regina Kropatsch 40,  Ingo Kurth 41,  Roman Chrast 42,  Tatsuo Michiue 3,  David L H Bennett 43,  C Geoffrey Woods 1,  Jan Senderek 4
Affiliations

Affiliations

  • 1 1] Department of Medical Genetics, University of Cambridge, Cambridge, UK. [2] Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
  • 2 Department of Orthopaedics, Medical University Vienna, Vienna, Austria.
  • 3 Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan.
  • 4 Friedrich-Baur-Institute, Ludwig Maximilians University Munich, Munich, Germany.
  • 5 1] Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. [2] Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
  • 6 1] Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany. [2] Institute of Human Genetics, Technische Universität München, Munich, Germany.
  • 7 Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
  • 8 Disease Mechanism Research Core, RIKEN Brain Science Institute, Saitama, Japan.
  • 9 Neusentis Research Unit, Pfizer, Cambridge, UK.
  • 10 1] Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. [2] School of Health and Rehabilitation Sciences, The University of Queensland, St. Lucia, Australia.
  • 11 Department of Neurology, Istanbul University, Istanbul, Turkey.
  • 12 Ambulantes Gesundheitszentrum der Charité Campus Virchow (Humangenetik), Universitätsmedizin Berlin, Berlin, Germany.
  • 13 1] Praxis für Humangenetik Cottbus, Cottbus, Germany. [2] Institut für Humangenetik, Universitätsklinikum Leipzig, Leipzig, Germany.
  • 14 1] Institut für Humangenetik, Universitätsklinikum Leipzig, Leipzig, Germany. [2] Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany.
  • 15 Department of Dermatology, Our Lady's Children's Hospital, Dublin, Ireland.
  • 16 Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
  • 17 Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.
  • 18 Neuropädiatrische Ambulanz, Krankenhaus der Barmherzigen Schwestern Linz, Linz, Austria.
  • 19 Neurogenetics Unit, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
  • 20 Departamento de Cirugía Plástica, Hospital Infantil Universitario de San José, Bogotá, Colombia.
  • 21 Unidad de Genética, Universidad del Rosario, Bogotá, Colombia.
  • 22 Institut für Neuropathologie, Uniklinik RWTH Aachen, Aachen, Germany.
  • 23 1] Friedrich-Baur-Institute, Ludwig Maximilians University Munich, Munich, Germany. [2] German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
  • 24 Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
  • 25 Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK.
  • 26 SPZ Neuropädiatrie Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • 27 CharitéCentrum für Zahn-, Mund- und Kieferheilkunde, Arbeitsbereich Kinderzahnmedizin, Universitätsmedizin Berlin, Berlin, Germany.
  • 28 GENDIA (GENetic DIAgnostic Network), Antwerp, Belgium.
  • 29 Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
  • 30 Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, UK.
  • 31 1] Department of Neurology, University of California San Francisco, San Francisco, California, USA. [2] Department of Neuroscience, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy.
  • 32 Department of Neurology and Neurophysiology, Our Lady's Children's Hospital, Dublin, Ireland.
  • 33 1] Department of Neurology, Adelaide &Meath Hospital, Dublin, Ireland. [2] Academic Unit of Neurology, Trinity College, Dublin, Ireland.
  • 34 1] Department of Dermatology, Our Lady's Children's Hospital, Dublin, Ireland. [2] Clinical Medicine, Trinity College, Dublin, Ireland.
  • 35 Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
  • 36 1] Center for Human Genetics, Bioscientia, Ingelheim, Germany. [2] Department of Medicine, Renal Division, Freiburg University Medical Center, Freiburg, Germany. [3] Center for Clinical Research, Freiburg University Medical Center, Freiburg, Germany.
  • 37 1] Friedrich-Baur-Institute, Ludwig Maximilians University Munich, Munich, Germany. [2] Medizinisch Genetisches Zentrum, Munich, Germany.
  • 38 1] Neurogenetics Group, VIB Department of Molecular Genetics, University of Antwerp, Antwerp, Belgium. [2] Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. [3] Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.
  • 39 MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, National Hospital for Neurology, London, UK.
  • 40 Department of Human Genetics, Ruhr-University Bochum, Bochum, Germany.
  • 41 Institute of Human Genetics, Jena University Hospital, Jena, Germany.
  • 42 1] Institute of Human Genetics, Technische Universität München, Munich, Germany. [2] Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. [3] Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • 43 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
PMID: 26005867 DOI: 10.1038/ng.3308
Abstract

Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal. New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP). Here we identified 10 different homozygous mutations in PRDM12 (encoding PRDI-BF1 and RIZ homology domain-containing protein 12) in subjects with CIP from 11 families. Prdm proteins are a family of epigenetic regulators that control neural specification and neurogenesis. We determined that Prdm12 is expressed in nociceptors and their progenitors and participates in the development of sensory neurons in Xenopus embryos. Moreover, CIP-associated mutants abrogate the histone-modifying potential associated with wild-type Prdm12. Prdm12 emerges as a key factor in the orchestration of sensory neurogenesis and may hold promise as a target for new pain therapeutics.

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