title: The molecular basis of low activity levels of coagulation factor VII: a Brazilian cohort.
abstract: Inherited factor VII (FVII) deficiency is the most common among the rare bleeding disorders. It is transmitted as an autosomal recessive inheritance, due to mutations in the FVII gene (F7). Molecular studies of FVII deficiency are rare in non-Caucasian populations. The aim of the study was to evaluate the molecular basis behind low levels of FVII activity (FVII:C) levels in a cohort of Brazilian patients. A total of 34 patients with low FVII levels were clinically evaluated and submitted to laboratory tests, among these, prothrombin time and FVII:C, with different thromboplastins. All exons and intron/exon boundaries of F7 were amplified and sequenced. A total of 14 genetic alterations were identified, of which six were described previously, c.1091G>A, c.1151C>T, c.-323_-313insCCTATATCCT, c.285G>A, c.525C>T, c.1238G>A and eight (54.0%) and eight were new, c.128G>A, c.252C>T, c.348G>A, c.417G>A, c.426G>A, c.745_747delGTG, c.843G>A and c.805+52C>T. In addition to the mutation c.1091G>A, known as FVII Padua, the mutation c.1151C>T also presented discrepant FVII:C levels when tested with human and rabbit brain thromboplastin. There was no association between phenotype and genotype. Most of the identified genetic alterations found were polymorphisms. Low levels of FVII:C in this population were mostly related to polymorphisms in F7 and associated with a mild clinical phenotype. Mutation c.1151C>T was associated with discrepant levels of FVII:C using different thromboplastins, such as reported with FVII Padua.
authors.affiliation: Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Minas Gerais, Brazil.
authors.forename: F Y
authors.initials: FY
authors.lastname: Rabelo
authors.affiliation: Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Minas Gerais, Brazil.
authors.forename: L L
authors.initials: LL
authors.lastname: Jardim
authors.affiliation: Hospital Naval Marcilio Rio de Janeiro, Brazil.
authors.forename: M B
authors.initials: MB
authors.lastname: Landau
authors.affiliation: Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: T
authors.initials: T
authors.lastname: Gadelha
authors.affiliation: Prefeitura Municipal de Contagem, Minas Gerais, Brazil.
authors.forename: M F B
authors.initials: MF
authors.lastname: Corrêa
authors.affiliation: University Hospital, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: I F M
authors.initials: IF
authors.lastname: Pereira
authors.affiliation: Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Minas Gerais, Brazil.
authors.forename: S M
authors.initials: SM
authors.lastname: Rezende
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001938:Brazil; D002648:Child; D015331:Cohort Studies; D005167:Factor VII / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D055815:Young Adult
chemical_list: D005167:Factor VII
keywords: bleeding; factor VII; gene; mutation; polymorphism