Abstract
Familial idiopathic basal ganglia calcification (FIBGC), also known as “Fahr’s disease,” is a neuropsychiatric disorder with motor and cognitive symptoms. It is characterized pathologically by bilateral calcification most commonly in the basal ganglia and also in other brain regions such as the thalamus and cerebellum. A recent report by Wang et al. (2012) discovered multiple families with FIBGC carrying mutations in the SLC20A2 gene, encoding the inorganic phosphate transporter PiT-2, which segregated in an autosomal dominant pattern. To understand further the role of SLC20A2 in FIBGC brain pathology, here we described the gene expression pattern across the whole brain for SLC20A2, using the Allen Institute Human Brain Atlas database. Microarray analysis provided evidence that the neuroanatomical pattern of expression for SLC20A2 is highest in the regions most commonly affected in FIBGC. Neuroanatomical regions that demonstrated high correlation or anti-correlation with SLC20A2 expression also showed a molecular network with potential to explain the limited neuroanatomical distribution of calcifications in IBGC. Lastly, these co-expression networks suggest additional further candidate genes for FIBGC.
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Note
In March, 2013, after this article was accepted, the Allen Human Brain Atlas added a new normalization to their array data analysis (http://help.brain-map.org/display/humanbrain/Documentation). After repeating our study, based at the new normalization, we found some differences from our first analysis, for the correlates (PCDH12, RHOBTB2, SLC16A5, NEHF, VAMP1. MMEL1, EPB41L3, IDH3G, FLJ43860, CD55, TTC39A) and anti-correlates (GABRA4, RIN1, KCTD1, GABRA2, KCNH3, RGS20, ITPKA, FAM171B, DPF1, ACRN1). Several genes are present in both lists and even some of the new genes listed share similar molecular pathways with the previous ones listed. This actually increases the number of candidates to be explored in familial basal ganglia calcification.
Acknowledgments
JRMO received specific training for the Allen Institute of Brain Science Atlas during the 1st Molecular Neuroanatomy Course provided by the AIBS and the Okinawa Institute of Science and Technology. This study received support from the John Simon Guggenheim Memorial Foundation, Conselho Nacional de Pesquisa, Tecnologia e Inovação (CNPq). We are indebted to Mark Ziats, from NIH, for a great review and nice inputs to this manuscript.
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ESM 1
Heat map of probes corresponding to the genes whose expression profile shows greater correlation and anticorrelation compared to SLC20A2. We used data from two donors, marked in orange and blue on the top line. Immediately below, we grouped similar neuroanatomical structures to better visualize the correlation between expression profiles. The regions of basal nuclei, thalamus, and cerebellum are highlighted. GP, globus pallidus; Cd, caudate nucleus; Pu, putamen; TH, thalamus; Dt, dentate nucleus. Available from: http://www.brain-map.org. This is an edited version. ©2012 Allen Institute for Brain Science. Allen Brain Atlas [Internet] (PNG 2.15 MB)
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da Silva, R.J.G., Pereira, I.C.L. & Oliveira, J.R.M. Analysis of Gene Expression Pattern and Neuroanatomical Correlates for SLC20A2 (PiT-2) Shows a Molecular Network with Potential Impact in Idiopathic Basal Ganglia Calcification (“Fahr’s Disease”). J Mol Neurosci 50, 280–283 (2013). https://doi.org/10.1007/s12031-013-0001-0
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DOI: https://doi.org/10.1007/s12031-013-0001-0