All these features also explain the high rate (up to 15-20%) of HAE-C1-INH cases with no family history of the disease (i.e. sporadic cases) that arise from de novo genetic variants in SERPING1. Deciphering whether a SERPING1 variant in a patient is inherited (transmitted by the parents) or de novo (occurring for the first time in the patient) is crucial for understanding the possible familial implications of the disease and for adequate genetic counseling. The gene discussed is SERPING1; the disease is hereditary angioedema.