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The Genetics of Primary Familial Brain Calcifications

  • Genetics (V Bonifati, Section Editor)
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Abstract

Bilateral accumulation of calcium in the brain, most commonly in the basal ganglia, but also in the cerebellum, thalamus, and brainstem can be inherited in an autosomal dominant fashion and is then referred to as primary familial brain calcifications (PFBC). Clinical manifestations include a spectrum of movement disorders and neuropsychiatric abnormalities. In the past 2 years, 3 genes have been identified to cause PFBC, (ie, SLC20A2, PDGFRB, and PDGFB). SCL20A2 encodes the Type III sodium-dependent inorganic phosphate (Pi) transporter 2 (PiT2) and, when mutated, uptake of Pi is severely impaired likely causing buildup of calcium phosphate. The second identified cause of PFBC is mutations in PDGFRB, which codes for platelet-derived growth factor receptor β (PDGF-Rβ). Interestingly, the third PFBC gene is PDGFB that encodes the ligand of PDGF-Rβ, which is secreted during angiogenesis to recruit pericytes, thereby implying impairment of the blood-brain barrier as a disease mechanism of PFBC.

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Conflict of Interest

Ana Westenberger has received an intramural grant from the Medical Genetics Priority Program from the University of Lübeck, Germany and a research grant from the Fritz Thyssen Foundation. Christine Klein has received an intramural grant from the Medical Genetics Priority Program from the University of Lübeck, Germany. Dr. Klein also is a board member of the Bachmann Strauss Dystonia and Parkinson’s Disease Foundation; SAB of VIB University of Leuven. She also has received consultancy fees as a medical advisor to Centogene. Dr. Klein has also received a Career development award from the Hermann and Lilly Schilling foundation, DFG, BMBF, EU, and honoraria for speaking at the Annual Meeting of the American Academy of Neurology.

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  1. Institute of Neurogenetics, University of Lübeck, Ratzeburger Allee 160, Lübeck, 23538, Germany

    Ana Westenberger & Christine Klein

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  1. Ana Westenberger
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Correspondence to Christine Klein.

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This article is part of the Topical Collection on Genetics

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Westenberger, A., Klein, C. The Genetics of Primary Familial Brain Calcifications. Curr Neurol Neurosci Rep 14, 490 (2014). https://doi.org/10.1007/s11910-014-0490-4

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