To figure out why five members of a Pakistani family can't sweat — a condition that can lead to heat intolerance and even death — researchers led by Niklas Dahl at Uppsala University performed a whole-genome analysis.
As they report in the Journal of Clinical Investigation, the researchers uncovered a homozygous missense mutation in ITPR2, which encodes the type 2 inositol 1,4,5-trisphosphate receptor. The mutation, the researchers found, affects the pore of the receptor and calcium ion release from the endoplasm reticulum. Additionally, mice lacking the protein had impaired sweating.
"The surprise was that a point mutation, not a large deletion, was enough to cause the human disorder," says co-author Katsuhiko Mikoshiba from the RIKEN Brain Science Institute in a statement.
While the inability to sweat is uncommon, Dahl notes that excessive sweating affects about 2 percent of the population. "Such symptoms may be alleviated by a drug that inhibits IP3R2. However," he adds, "IP3R2 is expressed in many tissues, and compounds must first be carefully evaluated in experimental models.