title: [Analysis of a consanguineous pedigree featuring hereditary coagulation factor Ⅴ deficiency].
abstract: OBJECTIVE
  To screen potential mutation and explore the underlying mechanism for a consanguineous pedigree featuring hereditary coagulation factor Ⅴ (FⅤ) deficiency.
  
  
  METHODS
  Clinical diagnosis was validated by coagulant parameter assays of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), FⅤ procoagulant activity (FⅤ:C) and FⅤ antigen (FⅤ:Ag). Potential mutations of the F5 gene in the proband and his family members were analyzed by direct DNA sequencing of PCR products of all exons, exon-intron boundaries and 3', 5' untranslated regions. Suspected mutation was confirmed by reverse sequencing.
  
  
  RESULTS
  The PT and APTT in the proband were significantly prolonged, which measured 23.5 s (reference range 11.8-14.8 s) and 50.5 s (reference range 27.0-41.0 s), respectively. FⅤ activity and FⅤ antigen of the proband were significantly reduced to 8% and <1%, respectively. PT and APTT in the younger sister of the proband were also significantly prolonged (24.1 s and 62.4 s, respectively). Her FⅤ activity and FⅤ antigen were also significantly decreased (7% and <1%, respectively). PT and APTT of other family members were within the normal range. The homozygous missence mutation causing T→C transition at position 29170 in exon 5 of F5 gene has resulted in a Phe190Ser substitution in the proband. His younger sister was also homozygous for Phe190Ser. Heterozygosity for Phe190Ser was confirmed in his elder brother, elder sister, two daughters and niece, and their FⅤ activity were slightly decreased (57%, 73%, 72%, 66% and 75%, respectively). A normal wild type was observed in two younger brothers of the proband, and their FⅤ activity and FⅤ antigen were in the normal range.
  
  
  CONCLUSIONS
  Homozygous missence mutation of Phe190Ser has been found in above family featuring hereditary FⅤ deficiency. The homozygous missence mutation was inherited from the parents by consanguineous marriage. Phe190Ser probably underlies may underlie the pathogenesis of hereditary FⅤ deficiency in this pedigree.
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Yao-sheng
authors.initials: YS
authors.lastname: Xie
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Li-qing
authors.initials: LQ
authors.lastname: Zhu
authors.forename: Yan-hui
authors.initials: YH
authors.lastname: Jin
authors.forename: Li-hong
authors.initials: LH
authors.lastname: Yang
authors.forename: Hai-xiao
authors.initials: HX
authors.lastname: Xie
authors.forename: Ming-shan
authors.initials: MS
authors.lastname: Wang
authors.forename: Xiao-li
authors.initials: XL
authors.lastname: Yang
mesh_terms: D000328:Adult; D003241:Consanguinity; D005165:Factor V / Q000235:genetics; D005166:Factor V Deficiency / Q000097:blood / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010314:Partial Thromboplastin Time; D010375:Pedigree; D011517:Prothrombin Time; D017422:Sequence Analysis, DNA
chemical_list: D005165:Factor V