title: Transcriptional regulator PRDM12 is essential for human pain perception.
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.
authors.affiliation: 1] Department of Medical Genetics, University of Cambridge, Cambridge, UK. [2] Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
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authors.affiliation: Department of Orthopaedics, Medical University Vienna, Vienna, Austria.
authors.forename: Michaela
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authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan.
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authors.affiliation: Friedrich-Baur-Institute, Ludwig Maximilians University Munich, Munich, Germany.
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authors.affiliation: Neusentis Research Unit, Pfizer, Cambridge, UK.
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authors.affiliation: Friedrich-Baur-Institute, Ludwig Maximilians University Munich, Munich, Germany.
authors.forename: Caecilia
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authors.affiliation: Department of Orthopaedics, Medical University Vienna, Vienna, Austria.
authors.forename: Maria
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authors.affiliation: Friedrich-Baur-Institute, Ludwig Maximilians University Munich, Munich, Germany.
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authors.affiliation: Friedrich-Baur-Institute, Ludwig Maximilians University Munich, Munich, Germany.
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authors.identifier: 0000000274509980
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authors.forename: Maria Roberta
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authors.identifier: 0000000256428378
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authors.affiliation: 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.
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mesh_terms: D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002522:Chlorocebus aethiops; D003241:Consanguinity; D005260:Female; D056726:Genetic Association Studies; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D055495:Neurogenesis; D009619:Nociceptors / Q000378:metabolism; D000699:Pain Insensitivity, Congenital / Q000235:genetics; D058748:Pain Perception; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D014982:Xenopus laevis
chemical_list: D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C587499:Prdm12 protein, human