title: [Novel double heterozygous mutations on Met306Val and Thr181Asn related to a hereditary coagulation factor VII deficiency].
abstract: OBJECTIVE
  To identify the genetic defect of coagulation factor VII in a Chinese family with hereditary FVII deficiency.
  
  
  METHODS
  Peripheral blood samples were collected from the proband of hereditary FVII deficiency, female, aged 15, 4 members of her family, and 100 healthy persons. Genomic DNA was isolated. All the exons and exon-intron boundaries of FVII gene were amplified by PCR, then the PCR products were sequenced by direct sequencing. Restrictive endonuclease analysis was performed in all of the family members and the 100 healthy donors to exclude gene polymorphism. Biostructural analysis of the mutated FVII was completed by molecular modeling.
  
  
  RESULTS
  Double heterozygous mutations in the proband were identified: A-->G mutation at position 10833 and C-->A mutation at position 9643, resulting in Met306Val and Thr181Asn substitution respectively. Heterozygosity for Met306Val was confirmed in the proband's mother and her elder sister; heterozygosity for Thr181Asn was confirmed in the proband's father. It was found by computer simulated molecular model that the Met306Val replacement, which was located on the surface of the FVII molecule, might cause steric hindrance and change the configuration and function of FVII protein.
  
  
  CONCLUSIONS
  Double heterozygous mutations for Met306Val and Thr181Asn in FVII gene have been found in a proband with hereditary FVII deficiency. The Met306Val substitution in FVII gene is a novel mutation in hereditary FVII deficiency. The heterozygous mutation of FVII gene may change the configuration of FVII protein and result in FVII dysfunction.
authors.affiliation: Department of Heamatology, Bao'an People's Hospital, Shenzhen 518101, China.
authors.forename: Chuan-qing
authors.initials: CQ
authors.lastname: Tu
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Deng
authors.forename: Jian-zeng
authors.initials: JZ
authors.lastname: Wu
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Pan
authors.forename: Chun-ying
authors.initials: CY
authors.lastname: Xie
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005167:Factor VII / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005168:Factor VII Deficiency / Q000097:blood / Q000235:genetics*; D005192:Family Health; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017434:Protein Structure, Tertiary
chemical_list: D005167:Factor VII