2024-03-29T11:35:58Z
https://soar-ir.repo.nii.ac.jp/oai
oai:soar-ir.repo.nii.ac.jp:00021349
2022-12-14T04:19:00Z
461:462
A Novel Mutation in the Fibrinogen Bβ Chain (c.490G>A; End of Exon 3) Causes a Splicing Abnormality and Ultimately Leads to Congenital Hypofibrinogenemia
Taira, Chiaki
Matsuda, Kazuyuki
Arai, Shinpei
Sugano, Mitsutoshi
Uehara, Takeshi
Okumura, Nobuo
hypofibrinogenemia
FGB
splicing abnormality
cryptic splice site
We found a novel heterozygous mutation in the fibrinogen Bβ chain (c.490G>A) of a 3-year-old girl with congenital hypofibrinogenemia. To clarify the complex genetic mechanism, we made a mini-gene including a FGB c.490G>A mutation region, transfected it into a Chinese Hamster Ovary (CHO) cell line, and analyzed reverse transcription (RT) products. The assembly process and secretion were examined using recombinant mutant fibrinogen. Direct sequencing demonstrated that the mutant RT product was 99 bp longer than the wild-type product, and an extra 99 bases were derived from intron 3. In recombinant expression, a mutant Bβ-chain was weakly detected in the transfected CHO cell line, and aberrant fibrinogen was secreted into culture media; however, an aberrant Bβ-chain was not detected in plasma. Since the aberrant Bβ-chain was catabolized faster in cells, the aberrant Bβ-chain in a small amount of secreted fibrinogen may catabolize in the bloodstream. FGB c.490G>A indicated the activation of a cryptic splice site causing the insertion of 99 bp in intron 3. This splicing abnormality led to the production of a Bβ-chain possessing 33 aberrant amino acids, including two Cys residues in the coiled-coil domain. Therefore, a splicing abnormality may cause impaired fibrinogen assembly and secretion.
Article
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES.18:2470(2017)
journal article
MDPI
2017-11-20
application/pdf
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
11
18
2470
1422-0067
AA12038549
https://soar-ir.repo.nii.ac.jp/record/21349/files/ijms-18-02470-v2.pdf
eng
29156616
https://www.ncbi.nlm.nih.gov/pubmed/29156616
10.3390/ijms18112470
https://doi.org/10.3390/ijms18112470
© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).