title: Coexistence of factor V G1691A and factor II G20210A gene mutations in a thrombotic family is associated with recurrence and early onset of venous thrombosis.
abstract: Two G-to-A mutations at positions 1691 of the factor V (FV) gene and 20210 of the prothrombin (FII) gene have been associated with an increased risk of venous thromboembolism. We report a thrombosis-prone family in which one subject--the propositus who exhibited combined heterozygous FV G1691A and FII G20210A mutations--showed spontaneous and early clinical onset (at 23 years), recurrences of deep-vein thrombosis and pulmonary embolism. His asymptomatic father carried the FII G20210A substitution and his mother, characterized by an isolated thrombotic episode on occasion of surgery (at 48 years), carried the FV G1691A substitution. In the maternal lineage, one of the propositus' uncles had thrombosis on occasion of a bone fracture (at 65 years) despite the absence of known prothrombotic defects. A sister of the propositus carried the FII G20210A and the brother the FV G1691A mutation. They have been asymptomatic until now. The propositus' two children, 20 and 16 years old, both carry the FV G1691A substitution and have been asymptomatic until now. The plasma levels of FII were higher in carriers of the FII G20210A allele if compared with noncarriers, and the activated protein C resistance phenotype, associated with the FV Leiden mutation, showed a complete correlation with the FV G1691A mutation. Despite the very limited number of thrombotic cases involved in this survey, which does not allow statistically sound conclusions, the data obtained from this family suggest that the synergy of inherited factors and transient risk conditions could play a key role in the occurrence of thrombotic accidents.
authors.affiliation: Centre for the Study of Haemostasis and Thrombosis, University of Ferrara, C. so Giovecca 203, I-44100 Ferrara, Italy. cet@unife.it
authors.forename: D
authors.initials: D
authors.lastname: Gemmati
authors.forename: M L
authors.initials: ML
authors.lastname: Serino
authors.forename: S
authors.initials: S
authors.lastname: Moratelli
authors.forename: S
authors.initials: S
authors.lastname: Tognazzo
authors.forename: A
authors.initials: A
authors.lastname: Ongaro
authors.forename: G L
authors.initials: GL
authors.lastname: Scapoli
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D004252:DNA Mutational Analysis; D005165:Factor V / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D011516:Prothrombin / Q000235:genetics*; D012008:Recurrence; D019851:Thrombophilia / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D020246:Venous Thrombosis / Q000235:genetics*
chemical_list: D005165:Factor V; D011516:Prothrombin