First Report of a de Novo Mutation at SLC20A2 in a Patient with Brain Calcification

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 similar to 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.FACEPEConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Pernambuco UFPE, Biol Sci Grad Program, Recife, PE, BrazilUniv Fed Pernambuco UFPE, Keizo Asami Lab LIKA, Recife, PE, BrazilUniversidade Federal de São Paulo UNIFESP, Lab Mol & Translat Endocrinol, São Paulo, BrazilHosp Serv Publ Estadual São Paulo, Neurosurg Residency Program, São Paulo, BrazilGoverno Estado Pernambuco, Forens Lab Social Def Secretary, Recife, PE, BrazilUniv Fed Pernambuco, Neuropsychiat Dept, BR-50670901 Recife, PE, BrazilAarhus Univ, Dept Mol Biol & Genet, Aarhus, DenmarkAarhus Univ, Dept Hematol, Aarhus, DenmarkAarhus Univ, Dept Clin Med, Aarhus, DenmarkUniversidade Federal de São Paulo UNIFESP, Lab Mol & Translat Endocrinol, São Paulo, BrazilFACEPE: APQ 1831-4.01/12CNPq: 457556/2013-7CNPq: 307909/2012-3CNPq: 400540/2013-4Web of Scienc