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Transcriptional regulator PRDM12 is essential for human pain perception.
- Source :
-
Nature genetics [Nat Genet] 2015 Jul; Vol. 47 (7), pp. 803-8. Date of Electronic Publication: 2015 May 25. - Publication Year :
- 2015
-
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.
- Subjects :
- Animals
COS Cells
Carrier Proteins metabolism
Chlorocebus aethiops
Consanguinity
Female
Genetic Association Studies
Hereditary Sensory and Autonomic Neuropathies genetics
Humans
Male
Mutation
Nerve Tissue Proteins metabolism
Neurogenesis
Nociceptors metabolism
Pain Insensitivity, Congenital genetics
Pedigree
Polymorphism, Single Nucleotide
Xenopus laevis
Carrier Proteins genetics
Nerve Tissue Proteins genetics
Pain Perception
Subjects
Details
- Language :
- English
- ISSN :
- 1546-1718
- Volume :
- 47
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Nature genetics
- Publication Type :
- Academic Journal
- Accession number :
- 26005867
- Full Text :
- https://doi.org/10.1038/ng.3308