Novel SLC20A2 mutations identified in southern Chinese patients with idiopathic basal ganglia calcification

Chen, Wan‐Jin; Yao, Xiang; Zhang, Qijie; Wang, Ni; He, J.; Li, Hongfu; Liu, Xin-Yi; Zhao, Guodong; Murong, Shen-Xing; Wang, Ning; Wu, Zhi‐Ying

doi:10.1016/j.gene.2013.07.071

Cited by 43 publications

(43 citation statements)

References 18 publications

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“…Functional studies in a Xenopus model showed impaired phosphate transport activity of PiT2 suggesting a loss-of-function disease mechanism [11]. Subsequent sequencing studies confirmed an important role for SLC20A2 in the etiology of IBGC, explaining up to 41% of familial cases [12–14] and 14% of sporadic cases[15]. …”

Section: Introductionmentioning

confidence: 99%

SLC20A2 and THAP1 deletion in familial basal ganglia calcification with dystonia

et al. 2013

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Idiopathic Basal Ganglia Calcification (IBGC) is characterized by bilateral calcification of the basal ganglia associated with a spectrum of neuropsychiatric and motor syndromes. In this study, we set out to determine the frequency of the recently identified IBGC gene SLC20A2 in 27 IBGC cases from the Mayo Clinic Florida Brain Bank using both Sanger sequencing and Taqman copy number analysis to cover the complete spectrum of possible mutations. We identified SLC20A2 pathogenic mutations in 2 of the 27 cases of IBGC (7%). Sequencing analysis identified a p.S113* nonsense mutation in SLC20A2 in one case. Taqman copy-number analysis of SLC20A2 further revealed a genomic deletion in a second case, which was part of a large previously reported Canadian IBGC family with dystonia. Subsequent whole-genome sequencing in this family revealed a 563,256 bp genomic deletion with precise breakpoints on chromosome 8 affecting multiple genes including SLC20A2 and the known dystonia related gene THAP1. The deletion co-segregated with disease in all family members. The deletion of THAP1 in addition to SLC20A2 in the Canadian IBGC family may contribute to the severe and early-onset dystonia in this family. The identification of a SLC20A2 genomic deletion in a familial form of IBGC demonstrates that reduced SLC20A2 in the absence of mutant protein is sufficient to cause neurodegeneration and that previously reported SLC20A2 mutation frequencies may be underestimated.

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Section: Introductionmentioning

confidence: 99%

SLC20A2 and THAP1 deletion in familial basal ganglia calcification with dystonia

et al. 2013

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“…This deletion comprised seven genes (VDAC3, SLC20A2, C8ORF40, CHRNB3, CHRNA6, THAP1, RNF170) and partial deletion of HOOK3; interestingly, THAP1 is the causative gene of a familial form of dystonia (DYT16), indeed the patients displayed dystonia as main symptom [24]. In two studies, mutations in the SLC20A2 gene have been found in 41 % of the familial PFBC cases and 14 % of sporadic patients, showing that PiT-2 impairment is a frequent and widespread cause of primary brain calcification [22,25].…”

Section: Slc20a2mentioning

confidence: 99%

Primary familial brain calcification: update on molecular genetics

et al. 2015

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Primary familial brain calcification is a neuropsychiatric disorder with calcium deposits in the brain, especially in basal ganglia, cerebellum and subcortical white matter. The disease is characterized by a clinical heterogeneity, with a various combination of symptoms that include movement disorders and psychiatric disturbances; asymptomatic patients have been also reported. To date, three causative genes have been found: SLC20A2, PDGFRB and PDGFB. SLC20A2 gene codes for the 'sodium-dependent phosphate transporter 2' (PiT-2), a cell membrane transporters of inorganic phosphate, involved in Pi uptake by cells and maintenance of Pi body levels. Over 40 pathogenic variants of SLC20A2 have been reported, affecting the regulation of Pi homeostasis. It was hypothesized that SLC20A2 mutations cause brain calcification most likely through haploinsufficiency. PDGFRB encodes for the platelet-derived growth factor receptor-β (PDGFRβ), a cell-surface tyrosine-kinase (RTK) receptor that regulates cell proliferation, migration, survival and differentiation. PDGFB encodes for the 'platelet-derived growth factor beta' (PDGFβ), the ligand of PDGFRβ. The loss of function of PDGFRβ and PDGFβ could lead to the impairment of the pericytes function and blood brain barrier integrity, causing vascular and perivascular calcium accumulation. SLC20A2 accounts for about 40 % of familial form and 14 % of sporadic cases, while PDGFRB and PDGFB mutations are likely rare. However, approximately 50 % of patients are not genetically defined and there should be at least another causative gene.

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“…In published studies, these three genes account for approximately 50% of cases [8,10,23,26,52,54,73,74]. However, in most of these studies, only the SLC20A2 gene was examined, and only by Sanger sequencing.…”

Section: Introductionmentioning

confidence: 99%