• Mark Estacion, Yang Yang, Sulayman D Dib-Hajj, Lynda Tyrrell, Zhimiao Lin, Yong Yang, and Stephen G Waxman.
• Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
• Biochem. Biophys. Res. Commun. 2013 Mar 1; 432 (1): 99-104.

AbstractGain-of-function missense mutations of SCN9A gene, which encodes voltage-gated sodium channel Nav1.7, alter channel's biophysical properties causing painful disorders which are refractory to pharmacotherapy in the vast majority of patients. Here we report a novel SCN9A mutation (ca.T3947C) in exon 20 in a 9 year old patient, not present in 200 ethnically-matched control alleles; the mutation substitutes the invariant valine 1316 residue within DIII/S5 by alanine (V1316A). Voltage-clamp studies show that Nav1.7 V1316A mutation hyperpolarizes activation (-9 mV), and enhances response to ramp stimuli (3-fold), changes that are predicted to cause hyperexcitability of DRG neurons. V1316A also hyperpolarizes steady-state slow-inactivation (-9.9 mV), which is predicted to attenuate the effect of this mutation on DRG neuron firing. These changes are consistent with previously characterized Erytheromelalgia associated mutations of Nav1.7.Copyright © 2013 Elsevier Inc. All rights reserved.

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