title: Activated protein C resistance due to a factor V mutation associated with familial ischemic stroke.
abstract: Recent findings have indicated the association between activated protein C (APC)-resistance and cerebrovascular disease. These reports prompted us to investigate whether resistance to APC could be found in patients suffering from transient ischaemic attacks or stroke. Therefore, we studied APC-resistance in 14 young adults belonging to three different families with a history of transient ischemic attacks (TIAs) and stroke. Nine out of fourteen subjects showed APC-resistance but no deficiencies in the anticoagulant proteins AT III, PC and PS. The family history demonstrated a distribution of APC-resistance compatible with dominant autosomal inheritance. A rapid screening method to detect factor V R506Q (Leiden) mutation without sequencing or restriction enzyme digestion has been set-up after biochemical analyses. DNA analysis showed a guanine to adenine transition at nucleotide 1,691 in patients and their relatives with poor response to activated protein C detected by APTT tests. Of 14 investigated subjects and their family members, 5 were normals, 6 were heterozygotes and 3 were homozygotes for factor V mutation. The mutation, in heterozygous form, was also found in 1.3% of our normal population (n = 75). Our findings indicate a possible involvement of APC-resistance in the pathogenesis of arterial thrombosis in young adults.
authors.affiliation: Institute of General Pathology and Oncology, II University of Naples, Italy.
authors.forename: D
authors.initials: D
authors.lastname: De Lucia
authors.forename: P
authors.initials: P
authors.lastname: Nina
authors.forename: M L
authors.initials: ML
authors.lastname: Papa
authors.forename: A
authors.initials: A
authors.lastname: Belli
authors.forename: M
authors.initials: M
authors.lastname: Conte
authors.forename: V
authors.initials: V
authors.lastname: Renis
authors.forename: C
authors.initials: C
authors.lastname: Di Mauro
authors.forename: S
authors.initials: S
authors.lastname: Masi
authors.forename: A
authors.initials: A
authors.lastname: Franco
authors.forename: G
authors.initials: G
authors.lastname: Schisano
mesh_terms: D000328:Adult; D001483:Base Sequence; D001780:Blood Coagulation Tests; D002545:Brain Ischemia / Q000097:blood / Q000235:genetics; D002561:Cerebrovascular Disorders / Q000097:blood / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D005091:Exons; D005165:Factor V / Q000032:analysis* / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D002546:Ischemic Attack, Transient / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D017354:Point Mutation; D011486:Protein C / Q000494:pharmacology*
chemical_list: D011486:Protein C; C095381:factor V Leiden; D005165:Factor V