| Literature DB >> 26005867 |
Ya-Chun Chen1, Michaela Auer-Grumbach2, Shinya Matsukawa3, Manuela Zitzelsberger4, Andreas C Themistocleous5, Tim M Strom6, Chrysanthi Samara7, Adrian W Moore8, Lily Ting-Yin Cho9, Gareth T Young9, Caecilia Weiss4, Maria Schabhüttl2, Rolf Stucka4, Annina B Schmid10, Yesim Parman11, Luitgard Graul-Neumann12, Wolfram Heinritz13, Eberhard Passarge14, Rosemarie M Watson15, Jens Michael Hertz16, Ute Moog17, Manuela Baumgartner18, Enza Maria Valente19, Diego Pereira20, Carlos M Restrepo21, Istvan Katona22, Marina Dusl4, Claudia Stendel23, Thomas Wieland24, Fay Stafford1, Frank Reimann25, Katja von Au26, Christian Finke27, Patrick J Willems28, Michael S Nahorski1, Samiha S Shaikh1, Ofélia P Carvalho1, Adeline K Nicholas29, Gulshan Karbani30, Maeve A McAleer15, Maria Roberta Cilio31, John C McHugh32, Sinead M Murphy33, Alan D Irvine34, Uffe Birk Jensen35, Reinhard Windhager2, Joachim Weis22, Carsten Bergmann36, Bernd Rautenstrauss37, Jonathan Baets38, Peter De Jonghe38, Mary M Reilly39, Regina Kropatsch40, Ingo Kurth41, Roman Chrast42, Tatsuo Michiue3, David L H Bennett43, C Geoffrey Woods1, Jan Senderek4.
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.Entities:
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Year: 2015 PMID： 26005867 PMCID： PMC7212047 DOI： 10.1038/ng.3308
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330