Inherited factor VII deficiency: identification of two novel mutations (A191V and T239P) in the catalytic domain.
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.
Borensztajn
Keren
K
INSERM U428, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris V, 4 avenue de l'Observatoire, 75270 Paris Cedex 06, France
Chafa
Ouerdia
O
Le Bonniec
Bernard
B
Wajcman
Henri
H
Reghis
Abderrezak
A
Fischer
Anne-Marie
AM
Tapon-Bretaudière
Jacqueline
J
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
D005167:Factor VII