A new SLC20A2 mutation identified in southern Italy family with primary familial brain calcification

Gagliardi, Monica; Morelli, Maurizio; Annesi, Grazia; Nicoletti, Giuseppe; Perrotta, Paolo; Pustorino, Giuseppe; Iannello, Grazia; Tarantino, Patrizia; Gambardella, Antonio; Quattrone, Aldo

doi:10.1016/j.gene.2015.05.005

Cited by 16 publications

(8 citation statements)

References 20 publications

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“…SLC20A2, located at 8p11.21, encodes the inorganic phosphate transporter PiT-2, a transmembrane protein associated with phosphate homeostasis in various tissues, including the brain, and its mutations result in a reduction of phosphate transport [38]. Mutations in SLC20A2 gene are responsible for most cases identified so far and over 40 pathogenic variants have been reported in patients with PFBC [46, 47]. Microarray analysis provided evidence that the neuroanatomical pattern of expression for SLC20A2 is highest in the regions most commonly affected in PFBC, showing that globus pallidus had the highest expression among basal ganglia, followed by thalamus and cerebellum [48].…”

Section: Classificationmentioning

confidence: 99%

Basal ganglia calcifications (Fahr’s syndrome): related conditions and clinical features

et al. 2019

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Basal ganglia calcifications could be incidental findings up to 20% of asymptomatic patients undergoing CT or MRI scan. The presence of neuropsychiatric symptoms associated with bilateral basal ganglia calcifications (which could occur in other peculiar brain structures, such as dentate nuclei) identifies a clinical picture defined as Fahr's Disease. This denomination mainly refers to idiopathic forms in which no metabolic or other underlying causes are identified. Recently, mutations in four different genes (SLC20A2, PDGFRB, PDGFB, and XPR1) were identified, together with novel mutations in the Myogenic Regulating Glycosylase gene, causing the occurrence of movement disorders, cognitive decline, and psychiatric symptoms. On the other hand, secondary forms, also identified as Fahr's syndrome, have been associated with different conditions: endocrine abnormalities of PTH, such as hypoparathyroidism, other genetically determined conditions, brain infections, or toxic exposure. The underlying pathophysiology seems to be related to an abnormal calcium/phosphorus homeostasis and transportation and alteration of the blood-brain barrier.

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Section: Classificationmentioning

confidence: 99%

Basal ganglia calcifications (Fahr’s syndrome): related conditions and clinical features

et al. 2019

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“… SLC20A2 (8p1.21) Encodes the inorganic phosphate transporter PiT-2, a transmembrane protein associated with phosphate homeostasis in various tissues, including the brain, and its mutations result in a reduction of phosphate transport. [10Mutations in SLC20A2 gene are responsible for most cases identified so far and over 40 pathogenic variants have been reported in patients with Farh's Disease [10] .Pattern of calcification: more severe calcification overwall in the lenticular, caudate, vermis, and subcortical white matter. DGFRB (5q32) and PDGFB (22q13.1) Are involved in pericytes recruitment, blood-brain barrier regulation, and angiogenesis [11 , [12] , [13] .Pattern of calcification: no calcification in vermis and cortical XPR1 (1q25.3) is a gene encoding a retroviral receptor with phosphate export function and involved in phosphate homeostasis [14] MYORG9p13.3 Identified as a novel genetic cause for autosomal-recessive PFBC in Chinese patients [15] , but its role in the pathogenesis of PFBC is yet unknown …”

Section: Discussionmentioning

confidence: 99%

Basal ganglia calcification: a Fahr's disease case report

Durante

Audino

Cristiano

et al. 2021

Radiology Case Reports

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Idiopathic basal ganglia calcification (IBGC), known as Fahr's disease, is a rare neurological disorder characterized by metabolic, biochemical, neuroradiological and neuropsychiatric alterations caused by symmetrical and bilateral intracranial calcifications. The disease has, in most cases, an autosomal dominant pattern of inheritance and genetic heterogeneity. Overlap of neuropsychiatric symptoms is common with movement disorders accounted for 55% of the manifestation. Here we present the case of a 58-year-old woman, presenting to the emergency department because of an accidental fall. Her past medical history was unremarkable and she denied any neurological symptoms a part from insomnia and anxiety. Patient was sent to the emergency department to perform a Brain Computed Tomography (CT) exam that showed bilateral symmetrical calcifications in cerebellar white matter, the corpus striatum, the posterior thalami, and the centrum semiovale of both cerebral hemispheres. Beeing a case of IBGC without relevant symptoms, diagnosis was mainly obtained thanks to the characteristics features of CT examination.

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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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A new SLC20A2 mutation identified in southern Italy family with primary familial brain calcification

Cited by 16 publications

References 20 publications

Basal ganglia calcifications (Fahr’s syndrome): related conditions and clinical features

Basal ganglia calcifications (Fahr’s syndrome): related conditions and clinical features

Basal ganglia calcification: a Fahr's disease case report

The Genetics of Primary Familial Brain Calcification: A Literature Review

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