Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis

  title={Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis},
  author={Cheng Wang and Yulei Li and Lei Shi and Jie Ren and Monica Patti and Tao Wang and Jo{\~a}o R M Oliveira and Mar{\'i}a Jes{\'u}s Sobrido and Beatriz Quint{\'a}ns and Miguel Baquero and Xiaoniu Cui and Xiang-yang Zhang and Lianqing Wang and Haibo Xu and Junhan Wang and Jing Yao and X Dai and Juan Liu and Lu Zhang and Hongying Ma and Yong Gao and Xixiang Ma and Shenglei Feng and Mugen Liu and Qing Kenneth Wang and Ian C. Forster and Xue Zhang and Jing-Yu Liu},
  journal={Nature Genetics},
Familial idiopathic basal ganglia calcification (IBGC) is a genetic condition with a wide spectrum of neuropsychiatric symptoms, including parkinsonism and dementia. Here, we identified mutations in SLC20A2, encoding the type III sodium-dependent phosphate transporter 2 (PiT2), in IBGC-affected families of varied ancestry, and we observed significantly impaired phosphate transport activity for all assayed PiT2 mutants in Xenopus laevis oocytes. Our results implicate altered phosphate… 

Loss of Function of Slc20a2 Associated with Familial Idiopathic Basal Ganglia Calcification in Humans Causes Brain Calcifications in Mice

It is shown that knockout of Slc20a2 in mice causes calcifications in the thalamus, basal ganglia, and cortex, demonstrating that reduced PiT2 expression alone can cause brain calcifications.

Novel SLC20A2 variant in a Japanese patient with idiopathic basal ganglia calcification-1 (IBGC1) associated with dopa-responsive parkinsonism

A 64-year-old Japanese IBGC1 patient with bilateral basal ganglia calcification carrying a novel SLC20A2 variant presents with dopa-responsive parkinsonism with decreased dopamine transporter (DAT) density in the bilateral striatum and decreased cardiac 123I-meta-iodobenzylguanidine uptake.

Clinical heterogeneity of primary familial brain calcification due to a novel mutation in PDGFB

Primary familial basalganglia calcification (PFBC) is an autosomal dominant neurodegenerative disorder characterized by bilateral cerebral calcification primarily affecting the basal ganglia.

Expanding the genetic spectrum of primary familial brain calcification due to SLC2OA2 mutations: a case series

Three variants in SLC20A2 are found in patients with PFBC associated to three different clinical phenotypes, one of which is novel and two were already described as variants of uncertain significance and confirmed the pathogenicity of these three variants.

Primary familial brain calcification in the ‘IBGC2’ kindred: All linkage roads lead to SLC20A2

The genetic cause of primary familial brain calcification in the ‘IBGC2’ kindred is elucidated.

Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification

It is demonstrated that mutations in SLC20A2 are a major cause of familial IBGC, and non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation.

Haploinsufficiency of the Primary Familial Brain Calcification Gene SLC20A2 Mediated by Disruption of a Regulatory Element

Exome sequencing data of 71 unrelated, genetically unexplained PFBC patients was analyzed with the aim to detect copy number variations that may disrupt the expression of core PFBC‐causing genes.

Primary familial brain calcification linked to deletion of 5’ noncoding region of SLC20A2

The aim of this study was to identify the causative gene defect in a Finnish PFBC family with three affected patients.

SLC20A2 mutation manifesting as very late-onset orofacial dyskinesia

Two patients with SLC20A2 mutations who developed very late-onset orofacial dyskinesia as their initial manifestation of PFBC are reported on.

A de novo nonsense PDGFB mutation causing idiopathic basal ganglia calcification with laryngeal dystonia

The first full demonstration of the de novo occurrence of an IBGC-causative mutation in a sporadic case is presented, reports the case of a 20-year-old woman who presented laryngeal dystonia revealing IBGC.



Genetic heterogeneity in familial idiopathic basal ganglia calcification (Fahr disease)

Evidence against linkage to IBGC1 is found in five of the six families supporting previous preliminary studies demonstrating genetic heterogeneity in familial IBGC.

Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification

It is found that IIAC was associated with mutations that inactivated ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), a cell surface enzyme that generates inorganic pyroph phosphate (PPi), a solute that regulates cell differentiation and serves as an essential physiologic inhibitor of calcification.

Familial idiopathic basal ganglia calcification: a challenging clinical–pathological correlation

Clinical, radiological and pathological studies of a patient with FIBGC, a right-handed male with a 50-year history of trunk, upper extremities and oral abnormal movements, who developed severe cognitive impairment and behavioral troubles with agitation and aggressiveness, are provided.

NT5E mutations and arterial calcifications.

Background Arterial calcifications are associated with increased cardiovascular risk, but the genetic basis of this association is unclear. Methods We performed clinical, radiographic, and genetic

Severe vascular disturbance in a case of familial brain calcinosis

It is suggested that severe vascular impairment and mild inflammation contribute to the slow but inexorable progression of hereditary brain calcinosis.

Genetic disorders of renal phosphate transport.

Several proteins in the kidney participate in reabsorption of urinary phosphate; the review describes mutations in the genes that encode these proteins, and the syndromes they produce.

Identification of a novel genetic locus on chromosome 8p21.1–q11.23 for idiopathic basal ganglia calcification

  • X. DaiYong Gao Jing Yu Liu
  • Biology
    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
  • 2010
A large Chinese family with autosomal dominant IBGC was characterized and a novel genetic locus was identified at the 8p21.1–q11.23 locus, which may lead to identification of a disease‐causing gene with IBGC.

What is and what is not 'Fahr's disease'.

  • B. Manyam
  • Medicine, Biology
    Parkinsonism & related disorders
  • 2005

The emerging role of phosphate in vascular calcification.

Vascular smooth muscle cells respond to elevated phosphate levels by undergoing an osteochondrogenic phenotype change and mineralizing their extracellular matrix through a mechanism requiring sodium-dependent phosphate cotransporters, thereby increasing susceptibility to calcification even at phosphate concentrations that are in the normal range.

Phosphate and cardiovascular disease.

Despite convincing epidemiologic connections between phosphate excess and cardiovascular disease, no clinical trials have been conducted to establish a causal relationship, and large, randomized trials with hard endpoints are urgently needed to prove or disprove the benefits and risks of therapy.