2024-03-29T09:28:43Z
https://soar-ir.repo.nii.ac.jp/oai
oai:soar-ir.repo.nii.ac.jp:00019015
2022-12-14T04:14:37Z
461:462
Genetic analyses of novel compound heterozygous hypodysfibrinogenemia, Tsukuba I: FGG c.1129+62_65 del AATA and FGG c.1299+4 del A
Mukai, Saki
Nagata, Kazuhiro
Ikeda, Minami
Arai, Shinpei
Sugano, Mitsutoshi
Honda, Takayuki
Okumura, Nobuo
© 2016, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Frameshift mutation
Hypodysfibrinogenemia
Splicing abnormality
gamma A-chain
gamma '-chain
Epub 2016 Nov 5
Introduction: Wefound a novel hypodysfibrinogenemia designated Tsukuba I caused by compound heterozygous nucleotide deletionswith FGG c. 1129+ 62_ 65 del AATA and FGG c. 1299+ 4 del A on different alleles. The former was deep in intron 8 of FGG (IVS-8 deletion) and the latter in exon 9 of FGG (Ex-9 deletion), which is translated for the gamma'-chain, but not the.A-chain. AWestern blot analysis of plasma fibrinogen from our patient revealed an aberrant gamma-chain that migrated slightly faster than the normal B beta-chain. Materials andmethods: To clarify the complex genetic mechanismunderlying Tsukuba I's hypodysfibrinogenemia induced by nucleotide deletions in two regions, we generated two minigenes incorporating each deletion region, transfected them into Chinese Hamster Ovary (CHO) cells, and analyzed RT-PCR products. We also established CHO cells producing the recombinant variant fibrinogen,gamma' 409.A (Ex-9 deletion). Results and conclusions: Minigene I incorporating the IVS-8 deletion showed two products: a normal splicing product and the unspliced product. Minigene II incorporating the Ex-9 deletion only produced the unspliced product. The established gamma' 409.A-CHOcells secreted variant fibrinogenmore effectively than normal fibrinogen. Therefore, the aberrant splicing products derived from the IVS-8 deletion cause hypofibrinogenemia most likely due to nonsense-mediated mRNA decay and the partial production of normal.A-and gamma'-chains; moreover, the Ex-9 deletion causes hypodysfibrinogenemia due to the absence of normal.A-and gamma'-chain production (hypofibrinogenemia) and augmented aberrant.'-chain production (dysfibrinogenemia). (C) 2016 Elsevier Ltd. All rights reserved.
Article
THROMBOSIS RESEARCH. 148:111-117 (2016)
PERGAMON-ELSEVIER SCIENCE LTD
2016-12
eng
journal article
AM
http://hdl.handle.net/10091/00019777
https://soar-ir.repo.nii.ac.jp/records/19015
https://pubmed.ncbi.nlm.nih.gov/27837696
27837696
https://doi.org/10.1016/j.thromres.2016.11.002
10.1016/j.thromres.2016.11.002
0049-3848
THROMBOSIS RESEARCH
148
111
117
https://soar-ir.repo.nii.ac.jp/record/19015/files/Genetic_analyses_of_novel_compound_heterozygous_hypodysfibrinogenemia.pdf
application/pdf
900.6 kB
2017-11-04