Functional Evaluation of PDGFB-variants in Idiopathic Basal Ganglia Calcification, Using Patient-derived IPS Cells

Overview

Journal Sci Rep

Specialty Science

Date 2019 Apr 7

PMID 30952898

Citations 4

Authors

Shin-Ichiro Sekine

Masayuki Kaneko

Masaki Tanaka

Yuhei Ninomiya

Hisaka Kurita

Masatoshi Inden

Megumi Yamada

Yuichi Hayashi

Takashi Inuzuka

Jun Mitsui

Hiroyuki Ishiura

Atsushi Iwata

Hiroto Fujigasaki

Hisamitsu Tamaki

Ryusei Tamaki

Shinsuke Kito

Yoshiharu Taguchi

Kortaro Tanaka

Naoki Atsuta

Gen Sobue

Takayuki Kondo

Haruhisa Inoue

Shoji Tsuji

Isao Hozumi

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

The Genetics of Primary Familial Brain Calcification: A Literature Review.

Chen S, Ho C, Lu Y, Lin C, Lan M, Tsai M Int J Mol Sci. 2023; 24(13).

PMID: 37446066 PMC: 10342144. DOI: 10.3390/ijms241310886.

Living with primary brain calcification with PDGFB variants: A qualitative study.

Takeuchi T, Aoyagi H, Kuwako Y, Hozumi I PLoS One. 2022; 17(10):e0275227.

PMID: 36206226 PMC: 9543980. DOI: 10.1371/journal.pone.0275227.

Case Report: Two Novel Frameshift Mutations in and One Novel Splice Donor Mutation in Associated With Primary Familial Brain Calcification.

Shen Y, Shu S, Ren Y, Xia W, Chen J, Dong L Front Genet. 2021; 12:643452.

PMID: 34025715 PMC: 8138311. DOI: 10.3389/fgene.2021.643452.

Partial reduced Pi transport function of PiT-2 might not be sufficient to induce brain calcification of idiopathic basal ganglia calcification.

Nishii K, Shimogawa R, Kurita H, Inden M, Kobayashi M, Toyoshima I Sci Rep. 2019; 9(1):17288.

PMID: 31754123 PMC: 6872723. DOI: 10.1038/s41598-019-53401-0.

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