2024-03-29T12:11:11Z
https://u-ryukyu.repo.nii.ac.jp/oai
oai:u-ryukyu.repo.nii.ac.jp:02012286
2023-08-03T05:31:20Z
1642838163960:1642838338003
1642838403551:1642838407795
Determination of the pathogenicity of known COL4A5 intronic variants by in vitro splicing assay
Horinouchi, Tomoko
Nozu, Kandai
Yamamura, Tomohiko
Minamikawa, Shogo
Nagano, China
Sakakibara, Nana
Nakanishi, Koichi
Shima, Yuko
Morisada, Naoya
Ishiko, Shinya
Aoto, Yuya
Nagase, Hiroaki
Takeda, Hiroki
Rossanti, Rini
Kaito, Hiroshi
Matsuo, Masafumi
Iijima, Kazumoto
X-linked Alport syndrome (XLAS) is a congenital renal disease caused by mutations in COL4A5. In XLAS cases suspected of being caused by aberrant splicing, transcript analysis needs to be conducted to determine splicing patterns and assess the pathogenicity. However, such analysis is not always available. We conducted a functional splicing assay using a hybrid minigene for seven COL4A5 intronic mutations: one was identified by us and six were found in the Human Gene Mutation Database. The minigene assay revealed exon skipping in four variants, exon skipping and a 10-bp insertion in one variant, and no change in one variant, which appeared not to be pathogenic. For one variant, our assay did not work. The results of all three cases for which transcript data were available were consistent with our assay results. Our findings may help to increase the accuracy of genetic test results and clarify the mechanisms causing aberrant splicing.
論文
http://purl.org/coar/resource_type/c_6501
Springer Nature
2019-09-03
VoR
http://hdl.handle.net/20.500.12000/45627
2045-2322
Scientific Reports
12696
9
eng
https://doi.org/10.1038/s41598-019-48990-9
https://doi.org/10.1038/s41598-019-48990-9
open access
Creative Commons Attribution 4.0 International License
http://creativecommons.org/licenses/by/4.0/