A new Nav1.7 mutation in an erythromelalgia patient

作者：Estacion, Mark; Yang, Yang; Dib-Hajj, Sulayman D.; Tyrrell, Lynda; Lin, Zhimiao; Yang, Yong; Waxman, Stephen G.^*

来源：Biochemical and Biophysical Research Communications, 2013, 432(1): 99-104.

DOI：10.1016/j.bbrc.2013.01.079

• Inherited neuropathy
• Channelopathy
• Pain
• Erythromelalgia
• Sodium channel

Gain-of-function missense mutations of SCN9A gene, which encodes voltage-gated sodium channel Na(v)1.7, 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 Na(v)1.7 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 Na(v)1.7.

• 出版日期2013-3-1
• 单位北京大学