Summary
We recently reported a high prevalence of the FV Leiden mutation (R506Q, responsible
for Activated Protein C resistance) among symptomatic protein C deficient probands
(19%), and the involvement of the FV Leiden mutation in the expression of thrombophilia
in six protein C deficient families. Here, we report the results of a similar study
in protein S deficient probands and families. Among 16 symptomatic protein S deficient
probands the prevalence of the FV Leiden mutation was high (38%). This high prevalence
is significantly different from that in the normal population, and is probably caused
by the selection of probands for familial thrombosis and protein S deficiency. In
4 families, the segregation of the FV Leiden mutation and the protein S deficiency
could be studied. In sibships where both abnormalities were segregating, the percentage
of symptomatic individuals with both abnormalities was 80%. Three of the seven subjects
with only the FV Leiden mutation, and two out of the three subjects with only protein
S deficiency had developed thrombosis. These results indicate that in the families
presented here the combination of the FV Leiden mutation and the protein S deficiency
is associated with a high risk for thrombosis. A reliable estimate of the penetrance
of the single defects is not possible, because the number of individuals with a single
defect is too low.
