COL18A1 and hereditary angioedema: 3.c.533G>A;p.(Gly178Asp) variant inherited in an autosomal-recessive pattern, suggested to be the disease-causing mutation when present in homozygous form—proband II.2 (family C) and proband II.1 (family D)—or in compound heterozygous form, for example, when combined with c.734C>T;p.(Thr245Met) for proband II.1, family A, or with c.582A>G;p.(Glu194=) for patient III.1, family C (Fig 1); the frequency of variant combinations is in agreement with the expected occurrence of HAE-nC1-INH;