Abstract
Primary familial brain calcification (PFBC) is identified by mineralization of the basal ganglia and other brain regions in the absence of known causes. The condition is often inherited in an autosomal dominant pattern and can manifest itself clinically with neuropsychiatric symptoms such as Parkinsonism, headaches, psychosis, and mood swings. Mutations in the SLC20A2 gene account for ~40 % of inherited cases, and this gene encodes an inorganic phosphate transporter (PiT-2), a transmembrane protein associated with Pi homeostasis. The p.Y386X mutation in SLC20A2 was identified in a patient who presented migraines, brain calcification, and mild but chronic hypovitaminosis D. SLC20A2 c.1158C > G single-nucleotide heterozygous mutation results in a premature stop codon and a putative truncated protein of 385 amino acids. Proband parents do not present the mutation, which is also not present in major public SNP databases, suggesting a de novo sporadic trait. This study describes for the first time a de novo SLC20A2 mutation in a PFBC patient with migraine and mild hypovitaminosis D. This data further reinforces the pathogenic role of SLC20A2 mutations as causal factors in PFBC physiopathology.
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Acknowledgments
We thank Ihgu Lucena and Dr. Juliana Machado for technical assistance with sample processing; FACEPE (APQ 1831-4.01/12) and CNPq (457556/2013-7;307909/2012-3;400540/2013-4) for the financial support; and Gaël Nicolas (Ruen University), Paula Sandrin, and Sérgio Crovella. J.B.F. and L.M.S. hold FACEPE and CAPES fellowships, respectively.
Conflict of interest
S.S., L.P., C.R., M.R.D.S., L.S., and J.R.M.O. work in public institution and did not receive any incentive from private companies. J.R.M.O. is the author of a book about familial brain calcification, edited by Nova Publishing (USA). J.F., L.P., M. K., R.R.L., M.F.O., N.J., and K.T. receive fellowships from graduate, undergraduate and post-graduate programs. The authors report no other disclosure and no conflict of interest directly linked to this report.
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Ferreira, J.B., Pimentel, L., Keasey, M.P. et al. First Report of a De Novo Mutation at SLC20A2 in a Patient with Brain Calcification. J Mol Neurosci 54, 748–751 (2014). https://doi.org/10.1007/s12031-014-0357-9
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DOI: https://doi.org/10.1007/s12031-014-0357-9