title: [Phenotypic detection and structure analysis of a PC missense mutation (Met406Ile) resulted in venous thromboembolism].
abstract: OBJECTIVE
  To identify the phenotypic detection and structure analysis of a protein C (PC) missense mutation (Met406Ile) resulting in venous thromboembolism.
  
  
  METHODS
  Pedigree research was performed for a hereditary PC deficiency pedigree. Chromogenic assay was used for phenotypic diagnosis to detect the AT activity. All 9 exons were amplified by polymerase chain reaction (PCR) and direct sequencing analysis was performed for PCR products. The corresponding mutation sites of family members were detected.Homology modeling was used for reconstructing mutant PC construction. The effects of construction change were analyzed.
  
  
  RESULTS
  The PC activities of proband and 4 family members decreased to different extents by 29.7%, 42.2%, 42.4%, 67.3% and 70.7% respectively. Among them, the proband and other three family members carried the same mutation (c.1218G > A, Met406Ile) while another family member had a PC polymorphism (rs1799810). Homology modeling showed that VDW's interaction radius of amino acids decreased after mutation (Met406Ile).In particular, the radius of Gly418:C and Ile406CG2, Gly418:C and Ile406HG23, Leu419:N and Ile406:HG23 decreased to 2.0733å, 1.620 45å and 1.446 52å respectively. Compared with normal PC, the interaction energy of mutant PC rose from -8.504 54 to 1210.04 kal/mol. And the change of VDW interaction energy was significant.
  
  
  CONCLUSIONS
  The mechanism of this pedigree is caused by PROC gene missense mutation on exon 9 (c.1218G > A, Met406Ile). The regional amino acids of mutant PC collide with each other and lead to an instability of PC reconstruction.
authors.affiliation: Department of Vascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.forename: Hao-yu
authors.initials: HY
authors.lastname: Deng
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.forename: Yi
authors.initials: Y
authors.lastname: Gu
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.forename: Ji-wei
authors.initials: JW
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D011486:Protein C / Q000235:genetics*; D054556:Venous Thromboembolism / Q000235:genetics*
chemical_list: D011486:Protein C