Transcriptional regulator PRDM12 is essential for human pain perception

Ya Chun Chen; Michaela Auer-Grumbach; Shinya Matsukawa; Manuela Zitzelsberger; Andreas C. Themistocleous; Tim M. Strom; Chrysanthi Samara; Adrian W. Moore; Lily Ting Yin Cho; Gareth T. Young; Caecilia Weiss; Maria Schabhüttl; Rolf Stucka; Annina B. Schmid; Yesim Parman; Luitgard Graul-Neumann; Wolfram Heinritz; Eberhard Passarge; Rosemarie M. Watson; Jens Michael Hertz; Ute Moog; Manuela Baumgartner; Enza Maria Valente; Diego Pereira; Carlos M. Restrepo; Istvan Katona; Marina Dusl; Claudia Stendel; Thomas Wieland; Fay Stafford; Frank Reimann; Katja Von Au; Christian Finke; Patrick J. Willems; Michael S. Nahorski; Samiha S. Shaikh; Ofélia P. Carvalho; Adeline K. Nicholas; Gulshan Karbani; Maeve A. McAleer; Maria Roberta Cilio; John C. McHugh; Sinead M. Murphy; Alan D. Irvine; Uffe Birk Jensen; Reinhard Windhager; Joachim Weis; Carsten Bergmann; Bernd Rautenstrauss; Jonathan Baets; Peter De Jonghe; Mary M. Reilly; Regina Kropatsch; Ingo Kurth; Roman Chrast; Tatsuo Michiue; David L H Bennett; C. Geoffrey Woods; Jan Senderek

doi:10.1038/ng.3308

Transcriptional regulator PRDM12 is essential for human pain perception

Ya Chun Chen, Michaela Auer-Grumbach, Shinya Matsukawa, Manuela Zitzelsberger, Andreas C. Themistocleous, Tim M. Strom, Chrysanthi Samara, Adrian W. Moore, Lily Ting Yin Cho, Gareth T. Young, Caecilia Weiss, Maria Schabhüttl, Rolf Stucka, Annina B. Schmid, Yesim Parman, Luitgard Graul-Neumann, Wolfram Heinritz, Eberhard Passarge, Rosemarie M. Watson, Jens Michael HertzUte Moog, Manuela Baumgartner, Enza Maria Valente, Diego Pereira, Carlos M. Restrepo, Istvan Katona, Marina Dusl, Claudia Stendel, Thomas Wieland, Fay Stafford, Frank Reimann, Katja Von Au, Christian Finke, Patrick J. Willems, Michael S. Nahorski, Samiha S. Shaikh, Ofélia P. Carvalho, Adeline K. Nicholas, Gulshan Karbani, Maeve A. McAleer, Maria Roberta Cilio, John C. McHugh, Sinead M. Murphy, Alan D. Irvine, Uffe Birk Jensen, Reinhard Windhager, Joachim Weis, Carsten Bergmann, Bernd Rautenstrauss, Jonathan Baets, Peter De Jonghe, Mary M. Reilly, Regina Kropatsch, Ingo Kurth, Roman Chrast, Tatsuo Michiue, David L H Bennett, C. Geoffrey Woods, Jan Senderek

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Abstract

© 2015 Nature America, Inc. All rights reserved.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.

Original language	English (US)
Pages (from-to)	803-808
Number of pages	6
Journal	Nature Genetics
Volume	47
Issue number	2015
DOIs	https://doi.org/10.1038/ng.3308
State	Published - Jan 1 2015

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Chen, Y. C., Auer-Grumbach, M., Matsukawa, S., Zitzelsberger, M., Themistocleous, A. C., Strom, T. M., Samara, C., Moore, A. W., Cho, L. T. Y., Young, G. T., Weiss, C., Schabhüttl, M., Stucka, R., Schmid, A. B., Parman, Y., Graul-Neumann, L., Heinritz, W., Passarge, E., Watson, R. M., ... Senderek, J. (2015). Transcriptional regulator PRDM12 is essential for human pain perception. Nature Genetics, 47(2015), 803-808. https://doi.org/10.1038/ng.3308

@article{f32b9c72e14846b0b50c63cc25180417,

title = "Transcriptional regulator PRDM12 is essential for human pain perception",

abstract = "{\textcopyright} 2015 Nature America, Inc. All rights reserved.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.",

author = "Chen, {Ya Chun} and Michaela Auer-Grumbach and Shinya Matsukawa and Manuela Zitzelsberger and Themistocleous, {Andreas C.} and Strom, {Tim M.} and Chrysanthi Samara and Moore, {Adrian W.} and Cho, {Lily Ting Yin} and Young, {Gareth T.} and Caecilia Weiss and Maria Schabh{\"u}ttl and Rolf Stucka and Schmid, {Annina B.} and Yesim Parman and Luitgard Graul-Neumann and Wolfram Heinritz and Eberhard Passarge and Watson, {Rosemarie M.} and Hertz, {Jens Michael} and Ute Moog and Manuela Baumgartner and Valente, {Enza Maria} and Diego Pereira and Restrepo, {Carlos M.} and Istvan Katona and Marina Dusl and Claudia Stendel and Thomas Wieland and Fay Stafford and Frank Reimann and {Von Au}, Katja and Christian Finke and Willems, {Patrick J.} and Nahorski, {Michael S.} and Shaikh, {Samiha S.} and Carvalho, {Of{\'e}lia P.} and Nicholas, {Adeline K.} and Gulshan Karbani and McAleer, {Maeve A.} and Cilio, {Maria Roberta} and McHugh, {John C.} and Murphy, {Sinead M.} and Irvine, {Alan D.} and Jensen, {Uffe Birk} and Reinhard Windhager and Joachim Weis and Carsten Bergmann and Bernd Rautenstrauss and Jonathan Baets and {De Jonghe}, Peter and Reilly, {Mary M.} and Regina Kropatsch and Ingo Kurth and Roman Chrast and Tatsuo Michiue and Bennett, {David L H} and Woods, {C. Geoffrey} and Jan Senderek",

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month = jan,

day = "1",

doi = "10.1038/ng.3308",

language = "English (US)",

volume = "47",

pages = "803--808",

journal = "Nature Genetics",

issn = "1061-4036",

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Chen, YC, Auer-Grumbach, M, Matsukawa, S, Zitzelsberger, M, Themistocleous, AC, Strom, TM, Samara, C, Moore, AW, Cho, LTY, Young, GT, Weiss, C, Schabhüttl, M, Stucka, R, Schmid, AB, Parman, Y, Graul-Neumann, L, Heinritz, W, Passarge, E, Watson, RM, Hertz, JM, Moog, U, Baumgartner, M, Valente, EM, Pereira, D, Restrepo, CM, Katona, I, Dusl, M, Stendel, C, Wieland, T, Stafford, F, Reimann, F, Von Au, K, Finke, C, Willems, PJ, Nahorski, MS, Shaikh, SS, Carvalho, OP, Nicholas, AK, Karbani, G, McAleer, MA, Cilio, MR, McHugh, JC, Murphy, SM, Irvine, AD, Jensen, UB, Windhager, R, Weis, J, Bergmann, C, Rautenstrauss, B, Baets, J, De Jonghe, P, Reilly, MM, Kropatsch, R, Kurth, I, Chrast, R, Michiue, T, Bennett, DLH, Woods, CG & Senderek, J 2015, 'Transcriptional regulator PRDM12 is essential for human pain perception', Nature Genetics, vol. 47, no. 2015, pp. 803-808. https://doi.org/10.1038/ng.3308

TY - JOUR

T1 - Transcriptional regulator PRDM12 is essential for human pain perception

AU - Chen, Ya Chun

AU - Auer-Grumbach, Michaela

AU - Matsukawa, Shinya

AU - Zitzelsberger, Manuela

AU - Themistocleous, Andreas C.

AU - Strom, Tim M.

AU - Samara, Chrysanthi

AU - Moore, Adrian W.

AU - Cho, Lily Ting Yin

AU - Young, Gareth T.

AU - Weiss, Caecilia

AU - Schabhüttl, Maria

AU - Stucka, Rolf

AU - Schmid, Annina B.

AU - Parman, Yesim

AU - Graul-Neumann, Luitgard

AU - Heinritz, Wolfram

AU - Passarge, Eberhard

AU - Watson, Rosemarie M.

AU - Hertz, Jens Michael

AU - Moog, Ute

AU - Baumgartner, Manuela

AU - Valente, Enza Maria

AU - Pereira, Diego

AU - Restrepo, Carlos M.

AU - Katona, Istvan

AU - Dusl, Marina

AU - Stendel, Claudia

AU - Wieland, Thomas

AU - Stafford, Fay

AU - Reimann, Frank

AU - Von Au, Katja

AU - Finke, Christian

AU - Willems, Patrick J.

AU - Nahorski, Michael S.

AU - Shaikh, Samiha S.

AU - Carvalho, Ofélia P.

AU - Nicholas, Adeline K.

AU - Karbani, Gulshan

AU - McAleer, Maeve A.

AU - Cilio, Maria Roberta

AU - McHugh, John C.

AU - Murphy, Sinead M.

AU - Irvine, Alan D.

AU - Jensen, Uffe Birk

AU - Windhager, Reinhard

AU - Weis, Joachim

AU - Bergmann, Carsten

AU - Rautenstrauss, Bernd

AU - Baets, Jonathan

AU - De Jonghe, Peter

AU - Reilly, Mary M.

AU - Kropatsch, Regina

AU - Kurth, Ingo

AU - Chrast, Roman

AU - Michiue, Tatsuo

AU - Bennett, David L H

AU - Woods, C. Geoffrey

AU - Senderek, Jan

PY - 2015/1/1

Y1 - 2015/1/1

N2 - © 2015 Nature America, Inc. All rights reserved.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.

AB - © 2015 Nature America, Inc. All rights reserved.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.

U2 - 10.1038/ng.3308

DO - 10.1038/ng.3308

M3 - Article

SN - 1061-4036

VL - 47

SP - 803

EP - 808

JO - Nature Genetics

JF - Nature Genetics

IS - 2015

ER -

Transcriptional regulator PRDM12 is essential for human pain perception

Abstract

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