title: Inherited factor VII deficiency: identification of two novel mutations (A191V and T239P) in the catalytic domain.
abstract: We describe here five F7 mutations found in four patients without bleeding history, despite constitutional coagulation Factor VII (FVII) deficiency. All five mutations are missense and affect the catalytic domain of FVII (A191T, A191V, T239P, R224Q and M298I). The A191V and T239P mutations are novel and were found in homozygous patients with no clinical bleeding tendency. The patient diagnosed with the A191V mutation had a phenotype corresponding to a moderate type 1 FVII deficiency (FVII:C 4%, FVII:Ag 5%). The T239P mutation was found in a patient with mild type 2 FVII deficiency (FVII:C 25%, FVII:Ag 95%). Novel mutations are both in close vicinity to the charge-stabilizing system of FVII. Modeling studies allow understanding in part the molecular basis for the loss of function.
authors.affiliation: INSERM U428, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris V, 4 avenue de l'Observatoire, 75270 Paris Cedex 06, France
authors.forename: Keren
authors.initials: K
authors.lastname: Borensztajn
authors.forename: Ouerdia
authors.initials: O
authors.lastname: Chafa
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Bonniec
authors.forename: Henri
authors.initials: H
authors.lastname: Wajcman
authors.forename: Abderrezak
authors.initials: A
authors.lastname: Reghis
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Fischer
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Tapon-Bretaudière
mesh_terms: D000328:Adult; D000462:Algeria; D020134:Catalytic Domain; D004252:DNA Mutational Analysis; D005167:Factor VII / Q000737:chemistry / Q000235:genetics; D005168:Factor VII Deficiency / Q000235:genetics*; D005260:Female; D006470:Hemorrhage / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D020125:Mutation, Missense; D017434:Protein Structure, Tertiary
chemical_list: D005167:Factor VII