A Nonsense Mutation in the SCN9A Gene in Congenital Insensitivity to Pain

Background: Congenital insensitivity to pain (CIP) (OMIM 243000) is a rare autosomal-recessive disorder. Clinically, CIP is characterized by insensitivity to all modalities of pain except neuropathic pain, and recurrent injuries frequently go unnoticed. CIP is caused by mutations in the SCN9A gene encoding for the Na1.7 channel. Methods: We analyzed the DNA from members of a consanguineous Pakistani family for mutations in the SCN9A gene through direct sequencing after performing linkage studies. Results: We identified a novel missense mutation designated R523X in all affected individuals. A screening assay ruled out the possibility of polymorphism. Conclusion: We identified a novel mutation in the Na1.7 channel leading to CIP, extending the spectrum of mutations in the Na1.7 channel, and enhancing our understanding of the physiology of pain. Copyright © 2010 S. Karger AG, Basel Received: April 8, 2010 Accepted after revision: April 29, 2010 Published online: July 13, 2010 Angela M. Christiano, PhD Department of Dermatology, Columbia University Russ Berrie Medical Center, 1150 St. Nicholas Avenue New York, NY 10032 (USA) Tel. +1 212 851 4850, Fax +1 212 851 4810, E-Mail amc65 @ columbia.edu © 2010 S. Karger AG, Basel Accessible online at: www.karger.com/drm D ow nl oa de d by : 54 .1 91 .4 0. 80 5 /1 /2 01 7 5: 40 :3 8 A M