A nonsense mutation in the SCN9A gene in congenital insensitivity to pain.

BACKGROUND Congenital insensitivity to pain (CIP) (OMIM 243000) is a rare autosomal-recessive disorder. Clinically, CIP is characterized by insensitivity to all modalities of pain except neuropathic pain, and recurrent injuries frequently go unnoticed. CIP is caused by mutations in the SCN9A gene encoding for the Na1.7 channel. METHODS We analyzed the DNA from members of a consanguineous Pakistani family for mutations in the SCN9A gene through direct sequencing after performing linkage studies. RESULTS We identified a novel missense mutation designated R523X in all affected individuals. A screening assay ruled out the possibility of polymorphism. CONCLUSION We identified a novel mutation in the Na1.7 channel leading to CIP, extending the spectrum of mutations in the Na1.7 channel, and enhancing our understanding of the physiology of pain.