| Title: |
Functional evaluation of PDGFB-variants in idiopathic basal ganglia calcification, using patient-derived iPS cells |
| Authors: |
Sekine, Shin-ichiro; Kaneko, Masayuki; Tanaka, Masaki; Ninomiya, Yuhei; Kurita, Hisaka; Inden, Masatoshi; Yamada, Megumi; Hayashi, Yuichi; Inuzuka, Takashi; Mitsui, Jun; Ishiura, Hiroyuki; Iwata, Atsushi; Fujigasaki, Hiroto; Tamaki, Hisamitsu; Tamaki, Ryusei; Kito, Shinsuke; Taguchi, Yoshiharu; Tanaka, Kortaro; Atsuta, Naoki; Sobue, Gen; Kondo, Takayuki; Inoue, Haruhisa; Tsuji, Shoji; Hozumi, Isao |
| Contributors: |
関根, 信一郎; 金子, 雅幸; 田中, 真生; 田中, 耕太郎; 栗田, 尚佳; 位田, 雅俊; 山田, 恵; 林, 祐一; 犬塚, 貴; 三井, 純; 石浦, 浩之; 岩田, 淳; 藤ヶ﨑, 浩人; 玉木, 久光; 鬼頭, 伸輔; 田口, 芳治; 熱田, 直樹; 祖父江, 元; 近藤, 孝之; 井上, 治久; 辻, 省次; 保住, 功; 70332327 |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2019 |
| Collection: |
Kyoto University Research Information Repository (KURENAI) / 京都大学学術情報リポジトリ |
| Subject Terms: |
Cellular neuroscience; Neurodegeneration |
| Description: |
Causative genes in patients with idiopathic basal ganglia calcification (IBGC) (also called primary familial brain calcification (PFBC)) have been reported in the past several years. In this study, we surveyed the clinical and neuroimaging data of 70 sporadic patients and 16 families (86 unrelated probands in total) in Japan, and studied variants of PDGFB gene in the patients. Variant analyses of PDGFB showed four novel pathogenic variants, namely, two splice site variants (c.160 + 2T > A and c.457−1G > T), one deletion variant (c.33_34delCT), and one insertion variant (c.342_343insG). Moreover, we developed iPS cells (iPSCs) from three patients with PDGFB variants (c.160 + 2T > A, c.457−1G > T, and c.33_34 delCT) and induced endothelial cells. Enzyme-linked immunoassay analysis showed that the levels of PDGF-BB, a homodimer of PDGF-B, in the blood sera of patients with PDGFB variants were significantly decreased to 34.0% of that of the control levels. Those in the culture media of the endothelial cells derived from iPSCs of patients also significantly decreased to 58.6% of the control levels. As the endothelial cells developed from iPSCs of the patients showed a phenotype of the disease, further studies using IBGC-specific iPSCs will give us more information on the pathophysiology and the therapy of IBGC in the future. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://hdl.handle.net/2433/250361; Scientific Reports; 5698 |
| Availability: |
https://hdl.handle.net/2433/250361 |
| Rights: |
© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Accession Number: |
edsbas.6DF3898C |
| Database: |
BASE |