IMR Press / FBL / Volume 21 / Issue 2 / DOI: 10.2741/4398

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.


Novel mutations in congenital factor XII deficiency

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1 Key Laboratory of Pediatric Hematology & Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai, China
2 Department of Pediatric surgery, Shanghai Children’s Medical Center, Shanghai, China
3 Departments of Clinical Laboratory, Xinhua Hospital, Shanghai, China
4 Departments of Clinical Laboratory, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Front. Biosci. (Landmark Ed) 2016, 21(2), 419–429;
Published: 1 January 2016
(This article belongs to the Special Issue Cellular immunology and stem cell biology)

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>A (p. G259E), c. 6658G>C (p. R267G) and c. 8489G>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.

Factor XII
Factor XII Deficiency
Blood Coagulation
Cross-Reactive Material-Negative
Dominant Negative
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