Induced pluripotent stem cells derived from a patient with familial idiopathic basal ganglia calcification (IBGC) caused by a mutation in SLC20A2 gene

Sekine, Shin-ichiro; Kondo, Takayuki; Murakami, Naotoshi; Imamura, Keiko; Enami, Takako; Shibukawa, Ran; Tsukita, Kayoko; Funayama, Misato; Inden, Masatoshi; Kurita, Hisaka; Inoue, Haruhisa

doi:10.1016/j.scr.2017.07.028

Cited by 4 publications

(3 citation statements)

References 3 publications

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“…SLC20A2 is the most common PFBC gene; heterozygous variants have been identified in more than 60% of genetically confirmed PFBC patients [ 3 ]. A missense change is the most common variant type, followed by frameshift, nonsense, and splice site variations, without obvious hotspots for pathogenic variants ( Figure 1 a) [ 3 , 6 , 7 , 17 , 18 , 21 , 23 , 37 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 ]. Functionally, both haploinsufficiency and dominant negative effects have been described; the loss of normal PiT2 function results in extracellular Pi accumulation and subsequent calcium phosphate formation [ 6 , 42 ].…”

Section: Genetics and Disease Mechanismmentioning

confidence: 99%

The Genetics of Primary Familial Brain Calcification: A Literature Review

Chen

et al. 2023

IJMS

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Primary familial brain calcification (PFBC), also known as Fahr’s disease, is a rare inherited disorder characterized by bilateral calcification in the basal ganglia according to neuroimaging. Other brain regions, such as the thalamus, cerebellum, and subcortical white matter, can also be affected. Among the diverse clinical phenotypes, the most common manifestations are movement disorders, cognitive deficits, and psychiatric disturbances. Although patients with PFBC always exhibit brain calcification, nearly one-third of cases remain clinically asymptomatic. Due to advances in the genetics of PFBC, the diagnostic criteria of PFBC may need to be modified. Hitherto, seven genes have been associated with PFBC, including four dominant inherited genes (SLC20A2, PDGFRB, PDGFB, and XPR1) and three recessive inherited genes (MYORG, JAM2, and CMPK2). Nevertheless, around 50% of patients with PFBC do not have pathogenic variants in these genes, and further PFBC-associated genes are waiting to be identified. The function of currently known genes suggests that PFBC could be caused by the dysfunction of the neurovascular unit, the dysregulation of phosphate homeostasis, or mitochondrial dysfunction. An improved understanding of the underlying pathogenic mechanisms for PFBC may facilitate the development of novel therapies.

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Section: Genetics and Disease Mechanismmentioning

confidence: 99%

The Genetics of Primary Familial Brain Calcification: A Literature Review

Chen

et al. 2023

IJMS

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“…Six of the patients who carried the SLC20A2 or PDGFB variants had participated and described in our previous studies, 11,12,16,21 and the cases were superscribed in Tables (Tables 3and4). Subsequently, the second survey was performed on these 27 patients with headaches to measure the intensity of their migraine using HIT-6 and MIDAS.…”

Section: Re Sultsmentioning

confidence: 99%

Evaluation of headaches in primary brain calcification in Japan

Kurita

Ozawa²,

Yamada

et al. 2021

Neurology & Clinical Neurosc

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Primary brain calcification (PBC) is also known as Fahr's disease, idiopathic basal ganglia calcification (IBGC), and primary familial brain calcification (PFBC). PBC is a rare neurodegenerative disorder characterized by bilateral calcification in the basal ganglia, cerebellar dentate nuclei, and thalami among others. Some of the patients, especially those with familial PBC, are found to have causative genes. Some PBC patients are asymptomatic, but for those with symptoms, their clinical manifestations widely vary, including parkinsonism, cerebellar symptoms, cognitive impairment, psychosis, seizures, or chronic headache. 1-3 PBC is defined with the differential diagnoses

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“…However, the genetic pathophysiological mechanisms and the calcification sites in mice were different from those of humans 5 . We produced iPS cells (iPSCs) from a patient with SLC20A2 variant 13 . New models of IBGC, including iPSCs, should be developed for further investigation, especially for drug treatment.…”

Section: Introductionmentioning

confidence: 99%

Functional evaluation of PDGFB-variants in idiopathic basal ganglia calcification, using patient-derived iPS cells

Sekine

Kaneko

Tanaka

et al. 2019

Sci Rep

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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.

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Induced pluripotent stem cells derived from a patient with familial idiopathic basal ganglia calcification (IBGC) caused by a mutation in SLC20A2 gene

Cited by 4 publications

References 3 publications

The Genetics of Primary Familial Brain Calcification: A Literature Review

The Genetics of Primary Familial Brain Calcification: A Literature Review

Evaluation of headaches in primary brain calcification in Japan

Functional evaluation of PDGFB-variants in idiopathic basal ganglia calcification, using patient-derived iPS cells

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