A de novo gain-of-function mutation in SCN11A causes loss of pain perception

Item Type:	Article
Title:	A de novo gain-of-function mutation in SCN11A causes loss of pain perception
Creators Name:	Leipold, E. and Liebmann, L. and Korenke, G.C. and Heinrich, T. and Giesselmann, S. and Baets, J. and Ebbinghaus, M. and Goral, R.O. and Stödberg, T. and Hennings, J.C. and Bergmann, M. and Altmüller, J. and Thiele, H. and Wetzel, A. and Nürnberg, P. and Timmerman, Vi. and De Jonghe, P. and Blum, R. and Schaible, H.G. and Weis, J. and Heinemann, S.H. and Hübner, C.A. and Kurth, I.
Abstract:	The sensation of pain protects the body from serious injury. Using exome sequencing, we identified a specific de novo missense mutation in SCN11A in individuals with the congenital inability to experience pain who suffer from recurrent tissue damage and severe mutilations. Heterozygous knock-in mice carrying the orthologous mutation showed reduced sensitivity to pain and self-inflicted tissue lesions, recapitulating aspects of the human phenotype. SCN11A encodes Na(v)1.9, a voltage-gated sodium ion channel that is primarily expressed in nociceptors, which function as key relay stations for the electrical transmission of pain signals from the periphery to the central nervous system. Mutant Na(v)1.9 channels displayed excessive activity at resting voltages, causing sustained depolarization of nociceptors, impaired generation of action potentials and aberrant synaptic transmission. The gain-of-function mechanism that underlies this channelopathy suggests an alternative way to modulate pain perception.
Keywords:	Action Potentials, Channelopathies, Gene Knock-In Techniques, Inbred C57BL Mice, NAV1.9 Voltage-Gated Sodium Channel, Nociceptors, Pain, Pain Perception, Animals, Mice
Source:	Nature Genetics
ISSN:	1061-4036
Publisher:	Nature Publishing Group
Volume:	45
Number:	11
Page Range:	1399-1404
Date:	November 2013
Official Publication:	https://doi.org/10.1038/ng.2767
PubMed:	View item in PubMed

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