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JAM2: A New Culprit at the Pathophysiology of Primary Familial Brain Calcification

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Abstract

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.

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References

  • Birbrair A, Zhang T, Wang Z-M, Messi ML, Mintz A, Delbono O (2015) Pericytes at the intersection between tissue regeneration and pathology. Clin Sci 128:81–93

    Article  CAS  Google Scholar 

  • Deng H, Zheng W, Jankovic J (2015) Genetics and molecular biology of brain calcification. Ageing Res Rev 22:20–38

    Article  CAS  Google Scholar 

  • Mochida GH, Ganesh VS, Felie JM, Gleason D, Hill RS, Clapham KR, Rakiec D, Tan W-H, Akawi N, Al-Saffar M (2010) A homozygous mutation in the tight-junction protein JAM3 causes hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. Am J Hum Genet 87:882–889

    Article  CAS  Google Scholar 

  • Obermeier B, Daneman R, Ransonhoff RM (2013) Development, maintenance and disruption of the blood–brain barrier. Nat Med 19:1584–1596

    Article  CAS  Google Scholar 

  • Quintáns B, Oliveira J, Sobrido MJ (2018) Primary familial brain calcifications. Handb Clin Neurol 147:307–317

    Article  Google Scholar 

  • Schottlaender LV, Abeti R, Jaunmuktane Z et al (2020) Bi-allelic JAM2 variants lead to early-onset recessive primary familial brain calcification. Am J Hum Genet 106(3):412–421. https://doi.org/10.1016/j.ajhg.2020.02.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vanlandewijck M, He L, Mäe M et al (2018) A molecular atlas of cell types and zonation in the brain vasculature. Nature 554:475–480

    Article  CAS  Google Scholar 

  • Yao X-P et al (2018) Biallelic Mutations in MYORG Cause Autosomal Recessive Primary Familial Brain Calcification. Neuron 98(6):1116-1123.e5

    Article  CAS  Google Scholar 

Download references

Funding

W.L.V.A.M. received a fellowship from Fundação de Amparo à Ciência e Tecnologia de Pernambuco (FACEPE; IBPG-0235–4.08/17).

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Correspondence to João Ricardo M. de Oliveira.

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The authors declare that ethics approval was not necessary for this manuscript, since it involves the discussion of theoretical aspects of data already published and available online.

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The data and material discussed here are available in the references listed.

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The authors declare that they have no competing interests or conflict, and no specific funding was used for the preparation of this text.

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Both authors contributed equally, and they acknowledge the support of two main Brazilian agencies: CNPq and FACEPE (IBPG-0234–4.08/17).

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Marinho, W.L.V.A., de Oliveira, J.R.M. JAM2: A New Culprit at the Pathophysiology of Primary Familial Brain Calcification. J Mol Neurosci 71, 1723–1724 (2021). https://doi.org/10.1007/s12031-021-01816-8

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  • DOI: https://doi.org/10.1007/s12031-021-01816-8

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