What Is The Underlying Genetic Cause Of Congenital Pain Insensitivity?
In the 1990s, a multi-national team of molecular geneticists discovered mutations in the gene known as NTRK1, also commonly referred to as TRKA, and proved that mutations in the NTRK1 gene are what causes CPI. The NTRK1 gene has been shown to encode the protein neurotrophic tyrosine kinase receptor type I. A normal, mutation-free copy of the NTRK1 gene encodes a normal copy of neurotrophic tyrosine kinase receptor type I, whereas mutant copies of the NTRK1 gene encode either no or defective copies of the neurotrophic tyrosine kinase receptor type I protein.
In healthy individuals, neurotrophic tyrosine kinase receptor type I helps support the survival of sympathetic ganglion neurons and nociceptive sensory neurons in dorsal root ganglia. Functioning sympathetic ganglion neurons are needed for, among other things, stimulating sweat glands to produce sweat, whereas nociceptive sensory neurons are involved in the sensing of noxious stimuli, such as those described above. Those who have two defective copies of the NTRK1 gene cannot synthesize functional neurotrophic tyrosine kinase receptor type I protein. Their sympathetic ganglion neurons and nociceptive sensory neurons in dorsal root ganglia therefore are prone to dying, which explains why they experience the symptoms that are described above.
There is no known cure for CPI. Typically, some symptoms, such as recurring fever and inability to sweat, for example, can be directly treated, but others, such as inability to sense noxious stimuli, for example, are not currently treatable. It is hoped, however, that better treatments courses will be developed as more is learned about CPI and the NTRK1 gene.