Elucidating the Genetic Basis of Common Variable Immune Deficiency in Simplex Cases

Though only one in 25,000 are diagnosed with common variable immune deficiency (CVID), it is the most common primary genetic immunodeficiency disease world-wide. The rare illness causes dangerously low levels of infection-fighting antibodies that, if left untreated, leads to recurrent infections that most others fight off with ease. The “variable” in the name refers to the fact that more than 10 different mutations have so far been found to trigger the disease, though these mutations only account for 10-20 percent of cases.

Attila Kumanovics, M.D., assistant professor of pathology, is leading a project to discover new mutations that cause CVID in the vast majority of patients. Most of these are suspected to be “simplex” cases caused by spontaneous mutations, rather than ones that have been passed down within a family for generations. 65 patients have already been recruited to take part in the study, which will focus on identifing causes of simplex cases of CVID.

First, investigators will use the Utah Population Database (UPDB) to determine whether any of the 65 CVID patients are related. Related patients will be further examined for mutations that cause familial forms of the disease. Among patients who are unrelated, the genomes of 20 of them, along with those of their parents, will be sequenced and analyzed in an effort to determine the genetic bases of simplex CVID. Identifying new CVID genes will lead to a better understanding of the biology behind the disease, new molecular diagnostic tests, better genetic counseling, and perhaps new conventional or gene-directed therapies.