RESUMEN
Primary familial brain calcification (PFBC) is an uncommon degenerative neurological disease that can be hereditary or sporadic, and manifests equally in both sexes and at any age. Several studies initially identified variants in four different genes as the cause of the disorder, all with an autosomal dominant inheritance pattern: SLC20A2, PDGFRB, PDGFB and XPR1. However, there have been reports of the involvement of additional genes in the autosomal recessive inheritance pattern, such as MYORG and more recently JAM2, suggesting that the deregulation of the neurovascular unit (NVU) is important in the pathogenesis of PFBC. The recent study by Schottlaender and collaborators (2020) has added new data to foster these analyses and to enable a better understanding of this underdiagnosed and intriguing neuropsychiatric condition. A great challenge now is to design a model that explains how different pathways might lead to similar neuroimaging findings but with variable clinical outcome, and with marked severity in cases linked to MYORG and JAM2. Currently available databases of detailed gene expression in different vascular cell types from the mouse brain could be used to explore a possible integrative model.
