Familial idiopathic basal ganglia calcification;
Bilateral striopallidodentate calcinosis (BSPDC);
Fahr disease

Familial idiopathic basal ganglia calcification (IBGC), also known as Fahr disease, is an inherited neurological disorder characterized by symmetric calcification in the basal ganglia and other brain regions, a wide spectrum of neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, seizures and chronic headache, and normal serum levels of calcium, phosphate, alkaline phosphatase and parathyroid hormone. The typical age at clinical onset is between 30 and 50 years, and most individuals affected with IBGC are asymptomatic during childhood and young adulthood. The diagnosis of IBGC generally relies on the visualization of bilateral calcification mainly in the basal ganglia by neuroimaging and the absence of metabolic, infectious, toxic, or traumatic causes. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. The mutations in SLC20A2 encoding type III sodium-dependent phosphate transporter 2 (PiT-2) are a major cause of familial IBGC. Recently the mutations of PDGFRB encoding platelet-derived growth factor (PDGF) receptor-beta, PDGFB encoding the PDGFR receptor-beta main ligand and XRP1 encoding a retroviral receptor have been reported to cause calcification in the brain.

Nervous system disease

SLC20A2 [HSA:6575] [KO:K14640]
PDGFRB [HSA:5159] [KO:K05089]
PDGFB [HSA:5155] [KO:K17386]
XPR1 [HSA:9213]

PMID:22327515

Wang C, Li Y, Shi L, Ren J, Patti M, Wang T, de Oliveira JR, Sobrido MJ, Quintans B, Baquero M, Cui X, Zhang XY, Wang L, Xu H, Wang J, Yao J, Dai X, Liu J, Zhang L, Ma H, Gao Y, Ma X, Feng S, Liu M, Wang QK, Forster IC, Zhang X, Liu JY

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

Nat Genet 44:254-6 (2012)
DOI:10.1038/ng.1077

PMID:23334463

Hsu SC, Sears RL, Lemos RR, Quintans B, Huang A, Spiteri E, Nevarez L, Mamah C, Zatz M, Pierce KD, Fullerton JM, Adair JC, Berner JE, Bower M, Brodaty H, Carmona O, Dobricic V, Fogel BL, Garcia-Estevez D, Goldman J, Goudreau JL, Hopfer S, Jankovic M, Jauma S, Jen JC, Kirdlarp S, Klepper J, Kostic V, Lang AE, Linglart A, Maisenbacher MK, Manyam BV, Mazzoni P, Miedzybrodzka Z, Mitarnun W, Mitchell PB, Mueller J, Novakovic I, Paucar M, Paulson H, Simpson SA, Svenningsson P, Tuite P, Vitek J, Wetchaphanphesat S, Williams C, Yang M, Schofield PR, de Oliveira JR, Sobrido MJ, Geschwind DH, Coppola G

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

Neurogenetics 14:11-22 (2013)
DOI:10.1007/s10048-012-0349-2

PMID:24463626

Yamada M, Tanaka M, Takagi M, Kobayashi S, Taguchi Y, Takashima S, Tanaka K, Touge T, Hatsuta H, Murayama S, Hayashi Y, Kaneko M, Ishiura H, Mitsui J, Atsuta N, Sobue G, Shimozawa N, Inuzuka T, Tsuji S, Hozumi I

Evaluation of SLC20A2 mutations that cause idiopathic basal ganglia calcification in Japan.

Neurology 82:705-12 (2014)
DOI:10.1212/WNL.0000000000000143

PMID:23255827

Nicolas G, Pottier C, Maltete D, Coutant S, Rovelet-Lecrux A, Legallic S, Rousseau S, Vaschalde Y, Guyant-Marechal L, Augustin J, Martinaud O, Defebvre L, Krystkowiak P, Pariente J, Clanet M, Labauge P, Ayrignac X, Lefaucheur R, Le Ber I, Frebourg T, Hannequin D, Campion D

Mutation of the PDGFRB gene as a cause of idiopathic basal ganglia calcification.

Neurology 80:181-7 (2013)
DOI:10.1212/WNL.0b013e31827ccf34

PMID:23913003

Keller A, Westenberger A, Sobrido MJ, Garcia-Murias M, Domingo A, Sears RL, Lemos RR, Ordonez-Ugalde A, Nicolas G, da Cunha JE, Rushing EJ, Hugelshofer M, Wurnig MC, Kaech A, Reimann R, Lohmann K, Dobricic V, Carracedo A, Petrovic I, Miyasaki JM, Abakumova I, Mae MA, Raschperger E, Zatz M, Zschiedrich K, Klepper J, Spiteri E, Prieto JM, Navas I, Preuss M, Dering C, Jankovic M, Paucar M, Svenningsson P, Saliminejad K, Khorshid HR, Novakovic I, Aguzzi A, Boss A, Le Ber I, Defer G, Hannequin D, Kostic VS, Campion D, Geschwind DH, Coppola G, Betsholtz C, Klein C, Oliveira JR

Mutations in the gene encoding PDGF-B cause brain calcifications in humans and mice.

Nat Genet 45:1077-82 (2013)
DOI:10.1038/ng.2723

PMID:25938945

Legati A, Giovannini D, Nicolas G, Lopez-Sanchez U, Quintans B, Oliveira JR, Sears RL, Ramos EM, Spiteri E, Sobrido MJ, Carracedo A, Castro-Fernandez C, Cubizolle S, Fogel BL, Goizet C, Jen JC, Kirdlarp S, Lang AE, Miedzybrodzka Z, Mitarnun W, Paucar M, Paulson H, Pariente J, Richard AC, Salins NS, Simpson SA, Striano P, Svenningsson P, Tison F, Unni VK, Vanakker O, Wessels MW, Wetchaphanphesat S, Yang M, Boller F, Campion D, Hannequin D, Sitbon M, Geschwind DH, Battini JL, Coppola G

Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export.

Nat Genet 47:579-81 (2015)
DOI:10.1038/ng.3289