A stop codon mutation in SCN9A causes lack of pain sensation

摘要: The general lack of pain experience is a rare occurrence in humans, and the molecular causes for this phenotype are not well understood. Here we have studied Canadian family from Newfoundland with members who exhibit congenital inability to pain. We mapped locus 13.7 Mb region on chromosome 2q (2q24.3-2q31.1). Screening candidate genes identified protein-truncating mutation SCN9A, which encodes voltage-gated sodium channel Na(v)1.7. C-A transversion at nucleotide 984 transforming codon tyrosine 328 stop codon. predicted product lacks all pore-forming regions Indeed, expression altered gene cell line did produce functional responses, nor it cause compensatory effects endogenous currents when expressed ND7/23 cells. Because homozygous knockout Na(v)1.7 mice has been shown be lethal, explored why deficiency non-lethal humans. Expression studies monkey, human, mouse rat tissue indicated species-differences profile. Whereas rodents was strongly hypothalamic nuclei, only weak mRNA levels were detected area primates. Furthermore, primate pituitary adrenal glands devoid signal, whereas these two mRNA-positive rodents. This species difference may explain non-lethality observed Our data further establish as critical element peripheral nociception