Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain disorders
Joost P.H. Drenth, Stephen G. Waxman
Joost P.H. Drenth, Stephen G. Waxman
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Science in Medicine

Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain disorders

Abstract

The voltage-gated sodium-channel type IX α subunit, known as Nav1.7 and encoded by the gene SCN9A, is located in peripheral neurons and plays an important role in action potential production in these cells. Recent genetic studies have identified Nav1.7 dysfunction in three different human pain disorders. Gain-of-function missense mutations in Nav1.7 have been shown to cause primary erythermalgia and paroxysmal extreme pain disorder, while nonsense mutations in Nav1.7 result in loss of Nav1.7 function and a condition known as channelopathy-associated insensitivity to pain, a rare disorder in which affected individuals are unable to feel physical pain. This review highlights these recent developments and discusses the critical role of Nav1.7 in pain sensation in humans.

Authors

Joost P.H. Drenth , Stephen G. Waxman

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Figure 4

Four clinical situations in which Nav1.7 channel activity is altered.

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Four clinical situations in which Nav1.7 channel activity is altered. ...
PE and PEPD are autosomal dominant (AD) conditions, while CIP is inherited via an autosomal recessive (AR) trait. The mutations of the Nav1.7 channel grossly dictate that there is a gain of function (increased channel activity) in PE and PEPD, while Nav1.7 channel function is lost (absent) in CIP. The resultant phenotype is reflected in the lower row. In humans, the Nav1.7 mutations result in pain in the feet and hands (in PE) or ocular, mandibular, and/or rectal pain (in PEPD). In CIP, there is a loss of Nav1.7 channel function, resulting in an inability to register pain.