title: A new Nav1.7 mutation in an erythromelalgia patient.
abstract: Gain-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.
authors: Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors: Mark
authors: M
authors: Estacion
authors: Yang
authors: Y
authors: Yang
authors: Sulayman D
authors: SD
authors: Dib-Hajj
authors: Lynda
authors: L
authors: Tyrrell
authors: Zhimiao
authors: Z
authors: Lin
authors: Yong
authors: Y
authors: Yang
authors: Stephen G
authors: SG
authors: Waxman
mesh_terms: D000409:Alanine / Q000235:genetics; D000595:Amino Acid Sequence; D002648:Child; D004916:Erythromelalgia / Q000235:genetics* / Q000503:physiopathology; D005091:Exons / Q000235:genetics; D005260:Female; D005727:Ganglia, Spinal / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000235:genetics* / Q000378:metabolism; D014633:Valine / Q000235:genetics
chemical_list: D062556:NAV1.7 Voltage-Gated Sodium Channel; C486866:SCN9A protein, human; D014633:Valine; D000409:Alanine