title: Primary familial brain calcification: update on molecular genetics.
abstract: 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.
authors: Department of Medicine, Surgery and Neurosciences, University of Siena, 53100, Siena, Italy, ilaria.taglia@gmail.com.
authors: Ilaria
authors: I
authors: Taglia
authors: Vincenzo
authors: V
authors: Bonifati
authors: Andrea
authors: A
authors: Mignarri
authors: Maria Teresa
authors: MT
authors: Dotti
authors: Antonio
authors: A
authors: Federico
mesh_terms: D001927:Brain Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D002114:Calcinosis / Q000235:genetics* / Q000473:pathology*; D016207:Cytokines / Q000235:genetics; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000235:genetics*; D014057:Tomography, X-Ray Computed; D014452:Ubiquitins / Q000235:genetics
chemical_list: D016207:Cytokines; C493589:SLC20A2 protein, human; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D014452:Ubiquitins; C074034:ISG15 protein, human; D020797:Receptor, Platelet-Derived Growth Factor beta