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Novel mutations in congenital factor XII deficiency.

Abstract
Several mutations in factor XII have been reported in patients with factor XII deficiency. Here, we described three mutations in the F12 gene (c. 6635G more than A (p. G259E), c. 6658G more than C (p. R267G) and c. 8489G more than A (p. E521K)) of five patients with congenital FXII deficiency. Among these, two were heterozygous mutations. All five patients had prolonged activated partial thromboplastin time, as well as markedly decreased FXII activity and antigen levels. In vitro studies in transiently transfected HEK 293T cells demonstrated that these mutations significantly lowered the FXII levels in the culture media, but had no impact on transcription. Further protein degradation inhibition experiments with various inhibitors suggested that the three mutants were degraded intracellularly through the proteasome pathway in the pre-Golgi compartment. Moreover, G259E and R267G mutations exhibited dominant negative effects, consistent with the phenotypes observed in the heterozygous carriers. Such dominant negative effects were not due to the dimerization of FXII. Our findings suggest that the three mutations in the F12 gene are the causing reasons for the cross-reactive material-negative FXII deficiencies.
AuthorsPeipei Jin, Wenli Jiang, Hui Yan, Lanbo Liu, Song Gu, Xuefeng Wang, Lisong Shen, Xi Mo
JournalFrontiers in bioscience (Landmark edition) (Front Biosci (Landmark Ed)) Vol. 21 Issue 2 Pg. 419-29 (01 01 2016) ISSN: 2768-6698 [Electronic] Singapore
PMID26709783 (Publication Type: Journal Article)
Chemical References
  • Factor XII
Topics
  • Adult
  • Child, Preschool
  • Factor XII (genetics)
  • Factor XII Deficiency (genetics)
  • Female
  • Genetic Carrier Screening
  • HEK293 Cells
  • Humans
  • Infant
  • Middle Aged
  • Mutation
  • Polymorphism, Single Nucleotide

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