Homozygotes for prothrombin gene 20210 A allele in a thrombophilic family without clinical manifestations of venous thromboembolism

Background and Objective. A new genetic risk factor for venous thromboembol ism has recently been described which involves a G to A transition at posit ion 20210 in the 3' untranslated region of the prothrombin gene. To date, o nly a few homozygotes for this mutation have been reported and in most of c ases, they suffered from thrombotic disease. Here, we describe a pedigree i ncluding both heterozygous and homozygous subjects for prothrombin (PT) 202 10 A. Design and Methods. This family was recruited in 1996 as part of our GAIT ( Genetic Analysis of Idiopathic Thrombophilia) project. To qualify for the G AIT study, a pedigree was required to have at least 10 living individuals i n three or more generations (i.e. extended pedigree). The pedigrees were se lected through probands with idiopathic thrombophilia. A complete set of pl asma and DNA determinations related to hemostasis was performed on this fam ily. Results. The plasma studies yielded normal results in all of the individual s. The family members who had a history of thromboembolism were heterozygou s carriers of the PT 20210 A variant. In addition, 4 relatives who were het erozygous, and two who were homozygous for this A allele, failed to show cl inical manifestations. These two homozygotes were 51 and 19 years old. Interpretation and Conclusions. This case exemplifies the complexity of thr ombotic disease since individuals homozygous for a mutant gene do not exhib it symp toms while heterozygous individuals often do exhibit the disease. T his case suggests that the new genetic risk factor for thrombosis (i.e. PT 20210 A) may not be as strong as most of the previously described genetic r isk factors. (C) 1999, Ferrata Storti Foundation.