title: Characterization of a Cys329Gly mutation causing hereditary factor VII deficiency.
abstract: We have previously reported a homozygous Cys329Gly mutation in a Chinese patient with factor VII (FVII) deficiency. Others have found a heterozygous Cys329Gly mutation in the F7 gene from patients of three different pedigrees. However, none of the reports included the expression and characterization of the mutant FVII in vitro. To investigate the effect of Cys329Gly on FVII function, we carried out transient transfections of baby hamster kidney cells (BHK-21) with a mutant FVII construct and compared the results to those obtained using a wild-type FVII construct and vector control. The results demonstrate that the level of FVII:Ag secreted into the medium by transfected BHK-21 cells with mutant construct was not affected, but the coagulation activity of the mutant FVII was undetectable. We conclude that Cys329 is critical to FVII coagulation, and the replacement of cysteine 329 by glycine leads to the loss of coagulation activity in the patients, possibly the molecular basis for FVII deficiency in the patients.
authors.affiliation: Medical Laboratory Center, Fuzhou General Hospital, Fuzhou, China. yuwu@ucalgary.ca
authors.forename: Yushui
authors.initials: Y
authors.lastname: Wu
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Tu
authors.forename: Yunzong
authors.initials: Y
authors.lastname: Lian
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Fenghua
authors.initials: F
authors.lastname: Lan
authors.forename: Zhongyong
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003545:Cysteine; D017931:DNA Primers; D005167:Factor VII / Q000235:genetics*; D005168:Factor VII Deficiency / Q000235:genetics*; D005260:Female; D005998:Glycine; D006801:Humans; D008297:Male; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D010375:Pedigree; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D005167:Factor VII; D003545:Cysteine; D005998:Glycine