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.
Highlights
Idiopathic basal ganglia calcification (IBGC), known as Fahr’s disease[1] or recently referred to as primary familial brain calcification (PFBC)[2], is a rare and intractable disease
The decrease in the production of platelet-derived growth factor (PDGF)-BB in endothelial cells may be a target for the therapy for patients with PDGFB variants
In this study we evaluated the level of PDGF-BB in sera and culture media of endothelial cells derived from iPS cells (iPSCs) of humans
Summary
Idiopathic basal ganglia calcification (IBGC), known as Fahr’s disease[1] or recently referred to as primary familial brain calcification (PFBC)[2], is a rare and intractable disease. It is characterized by abnormal deposits of minerals including calcium (Ca) in the basal ganglia and other brain regions, such as the thalamus and cerebellum. We developed iPSCs from patients with PDGFB variants and induced the endothelial cells. They mainly produce PDGF-BB which stimulates the pericytes in the brain. The decrease in the production of PDGF-BB in endothelial cells may be a target for the therapy for patients with PDGFB variants
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
