Transcriptional regulator PRDM12 is essential for human pain perception

• Published in: Nature genetics Vol. 47; no. 7; pp. 803 - 808
• Main Authors: Chen, Ya-Chun, Auer-Grumbach, Michaela, Matsukawa, Shinya, Zitzelsberger, Manuela, Themistocleous, Andreas C, Strom, Tim M, Samara, Chrysanthi, Moore, Adrian W, Cho, Lily Ting-Yin, Young, Gareth T, Weiss, Caecilia, Schabhüttl, Maria, Stucka, Rolf, Schmid, Annina B, Parman, Yesim, Graul-Neumann, Luitgard, Heinritz, Wolfram, Passarge, Eberhard, Watson, Rosemarie M, Hertz, Jens Michael, Moog, Ute, Baumgartner, Manuela, Valente, Enza Maria, Pereira, Diego, Restrepo, Carlos M, Katona, Istvan, Dusl, Marina, Stendel, Claudia, Wieland, Thomas, Stafford, Fay, Reimann, Frank, von Au, Katja, Finke, Christian, Willems, Patrick J, Nahorski, Michael S, Shaikh, Samiha S, Carvalho, Ofélia P, Nicholas, Adeline K, Karbani, Gulshan, McAleer, Maeve A, Cilio, Maria Roberta, McHugh, John C, Murphy, Sinead M, Irvine, Alan D, Jensen, Uffe Birk, Windhager, Reinhard, Weis, Joachim, Bergmann, Carsten, Rautenstrauss, Bernd, Baets, Jonathan, De Jonghe, Peter, Reilly, Mary M, Kropatsch, Regina, Kurth, Ingo, Chrast, Roman, Michiue, Tatsuo, Bennett, David L H, Woods, C Geoffrey, Senderek, Jan
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2015; Nature Publishing Group
• Subjects: 13; 13/100; 14/63; 38; 45; 45/23; 631/208/1516; 692/699/375/430; Agriculture; Animal Genetics and Genomics; Animals; Biomedical research; Biomedicine; Biopsy; Cancer Research; Carrier Proteins - genetics; Carrier Proteins - metabolism; Chlorocebus aethiops; Consanguinity; COS Cells; Epigenetics; Female; Gene Function; Gene mutations; Genes; Genetic aspects; Genetic Association Studies; Genetic regulation; Health aspects; Hereditary Sensory and Autonomic Neuropathies - genetics; Human Genetics; Humans; Identification and classification; letter; Male; Medical treatment; Medicin och hälsovetenskap; Mutation; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurogenesis; Nociception; Nociceptors - metabolism; Pain Insensitivity, Congenital - genetics; Pain Perception; Patients; Pedigree; Polymorphism, Single Nucleotide; Proteins; Stem cells; Studies; Xenopus laevis
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.3308

Geoffrey Woods, Jan Senderek and colleagues show that biallelic mutations in PRDM12 cause congenital insensitivity to pain. They further show that PRDM12 is expressed in nociceptors and their progenitors and participates in sensory neuron development in Xenopus . Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments 1 , 2 . In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal 3 , 4 . New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP) 5 , 6 . 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 7 , 8 . 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 9 , 10 .