Gene Variants Found in Hemolytic-Uremic Syndrome
Thrombomodulin variants impaired in their ability to inactivate the complement system
WEDNESDAY, July 22 (HealthDay News) -- About 5 percent of patients with atypical hemolytic-uremic syndrome have variants of the thrombomodulin gene that impair its ability to inactivate an immune pathway, according to a study in the July 23 issue of the New England Journal of Medicine.
Mieke Delvaeye, Ph.D., from VIB-K.U.Leuven Vesalius Research Center in Belgium, and colleagues sequenced the entire thrombomodulin gene in 152 patients with atypical hemolytic-uremic syndrome and 380 controls, and characterized the role of thrombomodulin in regulating the complement system.
The researchers identified six different heterozygous mutations in seven unrelated patients. Thrombomodulin normally negatively regulated complement by accelerating the inactivation of several complement components, which was impaired when using the variant versions of thrombomodulin.
"In conclusion, we have shown that thrombomodulin is a negative regulator of the complement system and that mutant variants of thrombomodulin may contribute to the development of atypical hemolytic-uremic syndrome," Delvaeye and colleagues write.