A family with factor XII deficiency: a family study suggesting that factor XII levels are determined by the presence of 3 codominant alleles with variable penetrance

We studied 15 members, in 3 generations of a family in whom the propositus had complete factor XII deficiency. The parents had factor XII levels of 59% and 62%. Three of the siblings had factor XII levels of less than 1%. Three more had factor XII levels of (30±5%). In 3 the levels ranged from (60-87%) and the remaining 2 siblings had levels exceeding 100%. The propositus with a level of less than 1% gave rise to an offspring with a level of 48%.

We propose that the gene controlling factor XII production consists of 3 separate alleles expressed codominantly: A - normal, B - low, O - absent. Members of the family with 100% factor XII activity have genotype AA; those with less than 1% activity have genotype OO; subjects with levels of 30% have genotype BO, and those with levels of 60% have genotype AO. We feel our study sheds new light on the inheritance of factor XII and the wide variation of levels in the general population.