title: Two double heterozygous mutations in the F7 gene show different manifestations.
abstract: We sequenced the factor VII gene (F7) in two unrelated Japanese patients with factor VII (FVII) deficiency. In the first (an asymptomatic 46-year-old man with FVII activity and antigen levels of 1.2% and 21% of normal respectively), novel E25K and H348Q mutations were identified in the doubly heterozygous state. In transiently transfected HEK293 cells, the level of FVII-E25K mutant activity in the culture media was significantly lower than that of FVII wild type, whereas the antigen levels of both proteins were similar. This suggests that the E25K mutation is associated with a dysfunctional FVII molecule. In the second patient (a 47-year-old woman with FVII activity and antigen levels of less than 1% and 6% respectively), an IVS4+1 mutation and a novel -96C to T transition were detected in the double heterozygous state. In electrophoretic mobility shift assays, the -96T mutation was shown to disrupt binding of Sp1.
authors.affiliation: Department of Laboratory Medicine, Tokyo Medical University, and First Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. keiring@rr.iij4u.or.jp
authors.forename: Keiko
authors.initials: K
authors.lastname: Nagaizumi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inaba
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hatta
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hagiwara
authors.forename: Kagehiro
authors.initials: K
authors.lastname: Amano
authors.forename: Morio
authors.initials: M
authors.lastname: Arai
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Fukutake
mesh_terms: D020134:Catalytic Domain; D004252:DNA Mutational Analysis; D005167:Factor VII / Q000235:genetics*; D005168:Factor VII Deficiency / Q000097:blood / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016297:Mutagenesis, Site-Directed; D010375:Pedigree; D017354:Point Mutation; D011487:Protein Conformation; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014162:Transfection
chemical_list: D016329:Sp1 Transcription Factor; D005167:Factor VII