title: [Identification of a novel mutation of factor XII gene in a family with coagulation FXII deficiency].
abstract: OBJECTIVE
  To analyze genetic mutation and molecular pathogenesis in a family affected with inherited coagulation factor XII(FXII) deficiency.
  
  
  METHODS
  Activated partial thromboplastin time (APTT), FXII procoagulant activity (FXII:C), FXII antigen (FXII:Ag) and other coagulants were measured. For affected members of the family, exons 1-14 and flanking intronic regions of the FXII gene were amplified with polymerase chain reaction (PCR) and sequenced thereafter. Expression plasmids containing mutant FXII cDNA was constructed and transfected into COS7 cells transiently. Expressions of FXII:Ag and FXII:C were analyzed.
  
  
  RESULTS
  The proband has manifested a prolonged APTT of 108.1 s (reference range: 27.0-41.0 s). Her husband has a normal APTT. Other members of the family had slightly increased APTT. The FXII:C and FXII:Ag of the proband have both dropped to about 0.01 (reference range: 0.72-1.13). The FXII:C levels of her husband, son, daughter and grandchild were 0.57, 0.24, 0.14, 0.16, respectively. And the FXII:Ag levels in her husband, son, daughter and grandchild were 0.55, 0.27, 0.15, 0.21, respectively. The proband and her daughter have both carried a heterozygous deletional mutation 6800-6808delAGCTGGGAG (6800-6808del9bp) in exon 9. For the promoter region of the FXII gene, the genotypes of the proband, her son, daughter and grandchild was TT, whilst that of her husband was CT. Expression study has shown that, whilst the mutant FXII protein has accumulated in the cells similar to wild-type protein, its secretion has reduced approximately by half.
  
  
  CONCLUSIONS
  A novel deletional mutation 6800-6808del9bp has been identified in the FXII gene. Although mutant FXII protein can still accumulate in cells, its secretion has become insufficient. The 6800-6808del9bp mutation and 46T/T have both contributed to the pathogenesis of FXII deficiency in the family, but may have not been the sole cause.
authors.affiliation: Diagnosis Center of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Haixiao
authors.initials: H
authors.lastname: Xie
authors.forename: Meiyan
authors.initials: M
authors.lastname: Lv
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yang
authors.forename: Liqing
authors.initials: L
authors.lastname: Zhu
authors.forename: Lihong
authors.initials: L
authors.lastname: Yang
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Jin
authors.forename: Mingshan
authors.initials: M
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D005174:Factor XII / Q000235:genetics* / Q000378:metabolism; D005175:Factor XII Deficiency / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D055815:Young Adult
chemical_list: D005174:Factor XII