Two novel SCN9A mutations causing insensitivity to pain

Abstract

The sensation of pain is important and there may be serious consequences if it is missing. Recently, the genetic basis for a channelopathy characterised by a congenital inability to experience pain has been described and channelopathy-associated insensitivity to pain has been proposed as a suitable name for this condition. Different mutations in the SCN9A gene causing loss of function of the voltage-gated sodium channel Nav1.7 have been reported in patients with this rare disease. Here we describe a woman with insensitivity to pain with two novel mutations in the SCN9A gene, coding for the Nav1.7 channel. We also discuss the finding of anosmia which apparently is a common feature in these patients.

Developments in autonomic research: a review of the latest literature

“…There is also a cluster of people with congenital insensitivity to pain in the far north of Sweden: in an upcoming issue of Neuroscience [2], Axellson and colleagues, from the Department of Laboratory Medicine at Lund University Hospital, Sweden, show that forearm skin biopsies taken from people with Norrbottnian congenital insensitivity to pain have essentially no sensory C-fibres that express the transient receptor potential (TRP) receptors-TRP vanilloid receptor type 1 (TRPV1), vanilloid 2 (TRPV2) and melastatin 8 (TRPM8). Finally, Nilsen and colleagues, from the Department of Neuroscience at the Norwegian University of Science and Technology in Trondheim, Norway, report in the May 2009 issue of Pain a woman with insensitivity to pain in whom two novel mutations in the SCN9A gene, which codes for a specific subunit of the voltage-gated sodium channel Na(v)1.7, were found [10]. Indeed, as described by Drenth and Waxman, of the Department of Medicine at the University Medical Center St. Radboud in Nijmegen, The Netherlands, in the December 2007 issue of the Journal of Clinical Investigation, disorders in the SCN9A gene have important consequences for the processing of nociceptive information: while nonsense mutations in Na(v)1.7 result in insensitivity to pain, gain-of-function missense mutations in Na(v) 1.7 have been shown to cause paroxysmal extreme pain disorder [6].…”

Distal Sensorimotor Neuropathy: Improvements in Diagnosis

“…Similarly, channelopathies leading to loss of function mutations may cause insensitivity to pain syndromes [153]. Polymorphisms in the adiponectin (ADPN) gene, T45G and G276T, have also recently been associated with increased risk of developing DSPN in type 2 diabetes [154].…”

Pharmacogenetics and Obstetric Anesthesia and Analgesia

“…In addition, a genetic database of knock-out mice allowing the study of genetic variations in the context of specific pain phenotypes was made public 49 . Recently an extremely rare phenotype characterized by a total absence of pain perception ('congenital indifference to pain') with no associated neuropathy has been associated with the mutations in the gene SCN9A, encoding the α-subunit of the voltage-gated sodium channel, Na v 1.7 [50][51][52] . Individuals with loss-of-function mutations of the Na V 1.7 lack protective mechanisms that allow tissue damage detection and suffer severe injuries because they do not learn pain-avoiding behaviors.…”