Novel mutations in congenital factor XII deficiency
| Autor: | Peipei Jin, Xi Mo, Xuefeng Wang, Wenli Jiang, Song Gu, Lanbo Liu, Hui Yan, Li-Song Shen |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Adult
Factor XII Factor XII Deficiency medicine.diagnostic_test Chemistry Genetic Carrier Screening HEK 293 cells Mutant Infant Transfection Middle Aged Polymorphism Single Nucleotide Molecular biology Phenotype In vitro HEK293 Cells Child Preschool Mutation medicine Humans Female Gene Partial thromboplastin time |
| Zdroj: | Frontiers in Bioscience. 21:419-429 |
| ISSN: | 1093-4715 1093-9946 |
| DOI: | 10.2741/4398 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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