These authors contributed equally to this manuscript.
Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations
Article first published online: 26 MAR 2007
2007 Blackwell Munksgaard
Volume 71, Issue 4, pages 311–319, April 2007
How to Cite
Goldberg, Y., MacFarlane, J., MacDonald, M., Thompson, J., Dube, M.-P., Mattice, M., Fraser, R., Young, C., Hossain, S., Pape, T., Payne, B., Radomski, C., Donaldson, G., Ives, E., Cox, J., Younghusband, H., Green, R., Duff, A., Boltshauser, E., Grinspan, G., Dimon, J., Sibley, B., Andria, G., Toscano, E., Kerdraon, J., Bowsher, D., Pimstone, S., Samuels, M., Sherrington, R. and Hayden, M. (2007), Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations. Clinical Genetics, 71: 311–319. doi: 10.1111/j.1399-0004.2007.00790.x
- Issue published online: 25 APR 2007
- Article first published online: 26 MAR 2007
- Received 5 January 2007, revised and accepted for publication 2 February 2007
- CIP (Congenital Indifference to Pain);
- sodium channel
Congenital indifference to pain (CIP) is a rare condition in which patients have severely impaired pain perception, but are otherwise essentially normal. We identified and collected DNA from individuals from nine families of seven different nationalities in which the affected individuals meet the diagnostic criteria for CIP. Using homozygosity mapping and haplotype sharing methods, we narrowed the CIP locus to chromosome 2q24–q31, a region known to contain a cluster of voltage-gated sodium channel genes. From these prioritized candidate sodium channels, we identified 10 mutations in the SCN9A gene encoding the sodium channel protein Nav1.7. The mutations completely co-segregated with the disease phenotype, and nine of these SCN9A mutations resulted in truncation and loss-of-function of the Nav1.7 channel. These genetic data further support the evidence that Nav1.7 plays an essential role in mediating pain in humans, and that SCN9A mutations identified in multiple different populations underlie CIP.