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Nat Genet. 2015 Jul;47(7):803-8. doi: 10.1038/ng.3308. Epub 2015 May 25.

Transcriptional regulator PRDM12 is essential for human pain perception.

Author information

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.

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.

PMID:
26005867
DOI:
10.1038/ng.3308
[Indexed for MEDLINE]

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