For example, affected members in the family with the F 12 Thr328Lys mutation, the I allele of ACE, and the A allele of rs3788853 at the XPNPEP2 locus of the APP gene never experienced angioedema during normal menstrual cycles; however, angioedema occurred during pregnancy within days of the first missed menstrual period, a time when estrogen levels would be only marginally higher than the end of a normal cycle. The gene discussed is APP; the disease is angioedema.