Homozygosity for a factor XII mutation in one female and one male patient with hereditary angio‐oedema

Hereditary angio‐oedema (HAE) with normal C1 inhibitor is associated with heterozygous mutations in the factor XII gene (FXII‐HAE). We report two Brazilian FXII‐HAE families segregating the mutation c.983 C>A (p.Thr328Lys). In each family, one patient with a homozygous mutation was found. The homozygous female patient in family 1 displayed a severe phenotype. However, this falls within the clinical phenotype spectrum reported for heterozygous female mutation carriers. The homozygous male patient in family 2 also showed a severe phenotype. This finding is intriguing, as to our knowledge, it is the first such report for a male FXII‐HAE mutation carrier. In the rare instances in which male mutation carriers are affected, a mild phenotype is typical. The present findings therefore suggest that homozygous FXII‐HAE mutation status leads to a severe phenotype in females and males, and to an increased risk of manifest symptoms in the latter.