title: [Molecular genetics and clinical features of nine patients with inherited coagulation factor VII deficiency].
abstract: OBJECTIVE
  To investigate potential mutations and clinical features of 9 unrelated patients with inherited coagulation factor VII (FVII) deficiency.
  
  
  METHODS
  Clinical diagnosis was validated by assaying of coagulation parameters including prothrombin time, activated partial thromboplastin time, FVII activity and specific antigens. All exons, exon-intron boundaries, and 5' and 3' untranslated regions of F7 genes were amplified with PCR. Potential mutations were detected by direct sequencing of purified PCR products. Suspected mutations were confirmed by sequencing of the opposite strand.
  
  
  RESULTS
  All probands have featured prolonged prothrombin time, with FVII activity ranging between 2.0% to 6.0%. The titers of FVII antigen were significantly reduced in 7 probands. Eight mutations, including 6 missense mutations, 1 deletion and 1 insertion, were identified, among which 3 (Gln100Leu, Ser269Pro and g.11520_11521insT) were not described previously. Six mutations have located in the protease domain. All mutations were inherited, and consanguineous marriages were reported in 5 families. Mutations g.27_28delCT, Cys329Gly, Arg304Trp and His348Gln have been identified in unrelated families. There was a lack of correlation between the mutations and their clinical features. Two individuals with homozygous His348Gln mutations and 1 individual with homozygous Arg304Trp mutation were only mildly affected or asymptomatic. Two patients, who have respectively carried homozygous and heterozygous deletions of g.27_28delCT, were moderately affected and asymptomatic. In 4 patients carrying double heterozygous mutations, 1 (Ser269Pro and Cys329Gly) was asymptomatic, 2 (Arg304Trp and Cys329Gly, Arg277Cys and g.11520_11521insT, respectively) had a mild bleeding tendency, whilst 1 (Gln100Leu and His348Gln) has a moderate bleeding diathesis.
  
  
  CONCLUSIONS
  There seem to be hotspots of F7 gene mutations in ethnic Han Chinese populations. And there is a lack of correlation between particular types of mutations and clinical phenotypes.
authors.affiliation: Wenzhou Medical College, Wenzhou, Zhejiang, People's Republic of China.
authors.forename: Yan-hui
authors.initials: YH
authors.lastname: Jin
authors.forename: Ming-shan
authors.initials: MS
authors.lastname: Wang
authors.forename: Fang-xiu
authors.initials: FX
authors.lastname: Zheng
authors.forename: Yao-sheng
authors.initials: YS
authors.lastname: Xie
authors.forename: Hai-xiao
authors.initials: HX
authors.lastname: Xie
authors.forename: Peng-fei
authors.initials: PF
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D025861:Blood Coagulation Disorders, Inherited / Q000235:genetics*; D002648:Child; D005167:Factor VII / Q000235:genetics*; D005168:Factor VII Deficiency / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D055815:Young Adult
chemical_list: D005167:Factor VII