2024-03-29T13:22:59Z
https://soar-ir.repo.nii.ac.jp/oai
oai:soar-ir.repo.nii.ac.jp:00003835
2022-12-14T04:39:56Z
461:462
Heterozygous B beta-chain C-terminal 12 amino acid elongation variant, B beta X462W (Kyoto VI), showed dysfibrinogenemia
Okumura, Nobuo
Terasawa, Fumiko
Takezawa, Yuka
Hirota-Kawadobora, Masako
Inaba, Tohru
Fujita, Naohisa
Saito, Masazumi
Sugano, Mitsutoshi
Honda, Takayuki
This is a non-final version of an article published in final form in BLOOD COAGULATION & FIBRINOLYSIS. 23(1):87-90 (2012)
albumin-binding form
B beta-chain
dysfibrinogen
variant dimeric fibrinogen
A heterozygous patient with dysfibrinogenemia with slight bleeding and no thrombotic complications was diagnosed with fibrinogen Kyoto VI (K-VI). To elucidate the genetic mutation(s) and characterize the variant protein, we performed the following experiments and compared with identical and similar variants that have already been reported. The proposita's PCR-amplified DNA was analyzed by sequencing and her purified plasma fibrinogen underwent SDS-PAGE followed by immunoblotting, fibrin polymerization, and scanning electron microscopic observation of fibrin clot and fibers. Sequence analyses showed that K-VI fibrinogen substituted W (TGG) for terminal codon (TAG), resulting in 12 amino acid elongation 462-473 (WSPIRRFLLFCM) in the B beta-chain. Protein analyses indicated that the presence of some albumin-binding variant fibrinogens and a dimeric molecule of variant fibrinogens reduced fibrin polymerization, with a thinner fiber and aberrant fibrin network. These results are almost the same as for the identical variant of Magdeburg, however, different from the similar variant of Osaka VI [ 12 amino acid elongation 462-473 (KSPIRRFLLFCM) in the B beta-chain] in the presence of variant forms and clot structure. We speculate the side-chain difference at 462 residues, W in K-VI, K in Osaka VI, and/or the difference in the presence of disulfide bridged forms of variant fibrinogens, led to the notable difference in the fibrin bundle network. Although a strong evolutional and structural association between B beta-chain and gamma-chain molecules is established, the corresponding recombinant 15 residue elongation variants of the fibrinogen gamma-chain showed reduced assembly and secretion.
Article
BLOOD COAGULATION & FIBRINOLYSIS. 23(1):87-90 (2012)
LIPPINCOTT WILLIAMS & WILKINS
2012-01
eng
journal article
AM
http://hdl.handle.net/10091/16227
https://soar-ir.repo.nii.ac.jp/records/3835
https://pubmed.ncbi.nlm.nih.gov/22001526
22001526
https://doi.org/10.1097/MBC.0b013e32834cb243
10.1097/MBC.0b013e32834cb243
0957-5235
AA10794937
BLOOD COAGULATION & FIBRINOLYSIS
23
1
87
90
https://soar-ir.repo.nii.ac.jp/record/3835/files/Heterozygous_B_beta-chain_C-terminal_12_amino_acid_elongation_variant.pdf
application/pdf
303.4 kB
2015-09-24