title: [Analysis of an hereditary protein C deficiency pedigree with compound heterozygous gene mutations].
abstract: OBJECTIVE
  To analyze genetic mutations and explore its molecular pathogenesis for an hereditary protein C (PC) deficiency pedigree.
  
  
  METHODS
  The pedigree has included 15 individuals from 4 generations. Plasma levels of PC activity (PC:A), PC antigen (PC:Ag) and other coagulant parameters were determined for members of the family. The 9 exons and intron-exon boundaries of protein C gene (PROC) of the proband were amplified with PCR and analyzed with direct sequencing. Detected mutations were confirmed with reverse sequencing. Corresponding PCR fragments from the family members were also directly sequenced.
  
  
  RESULTS
  Plasma PC:A and PC:Ag for the proband was 26% and 18.60%, respectively, both being lower than normal references. Seven members from the pedigree also had lower PC:A, six had lower PC:Ag. A compound heterozygous missense mutation, including a T to G transition at position 6128 of exon 7, which results in Phe139Val, and a G to C transition at position 8478 in exon 9, which results in Asp255His, were identified in the proband. The paternal grandma, father and two aunts were heterozygous for g.6128 T to G, whilst the mother, the second uncle, sister and son were heterozygous for g.8478 G to C. There were lower PC:A in family members with g.8478 G to C.
  
  
  CONCLUSIONS
  The proband had inherited two independent mutations of the PROC gene including g.6128 T to G in exon 7 and g.8478 G to C in exon 9 from her father and mother, respectively. The resulting compound heterozygous mutation has caused a serious hereditary protein C deficiency.
authors.affiliation: Wenzhou Medical College, Wenzhou, Zhejiang, People's Republic of China.
authors.forename: Li-hong
authors.initials: LH
authors.lastname: Yang
authors.forename: Li-qing
authors.initials: LQ
authors.lastname: Zhu
authors.forename: Xia-oli
authors.initials: XO
authors.lastname: Yang
authors.forename: Ming-shan
authors.initials: MS
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Bi-cheng
authors.initials: BC
authors.lastname: Chen
authors.forename: Yan-hui
authors.initials: YH
authors.lastname: Jin
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Fang-xiu
authors.initials: FX
authors.lastname: Zheng
mesh_terms: D006801:Humans; D009154:Mutation; D010375:Pedigree; D011486:Protein C / Q000235:genetics*; D020151:Protein C Deficiency / Q000235:genetics*
chemical_list: D011486:Protein C