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A novel SLC20A2 gene mutation causing primary familial brain calcification in an Ukrainian patient

  • Mariano Oliva
  • Guglielmo Capaldo
  • Alessandra D’Amico
  • Davide Colavito
  • Andrea Elefante
  • Giulia Straccia
  • Lorenzo Ugga
  • Gianfranco PuotiEmail author
Letter to the Editor
  • 61 Downloads

Dear Editor,

Primary familial brain calcification (PFBC) is a rare neurological disease characterized by symmetrical bilateral calcifications, which are mostly located in the basal ganglia but can also be detected in other areas of the brain [1]. The estimated prevalence of PFBC is < 1/1.000.000 [2], with a male:female ratio of about 2:1 [3]. Although symmetrical brain calcifications are frequently observed in routine CT scans [4], the disease usually begins in the fourth or fifth decade of life with a variable association of psychiatric symptoms, cognitive decline, and extrapyramidal syndrome. These cardinal aspects can also be accompanied by a broad constellation of other clinical features and, depending on the prevalent location of the calcium deposits, they include headache [5], seizures, ataxia and dysarthria [3], and transient ischemic attack or stroke [6]. On the other hand, a significant proportion of patients are asymptomatic at the time of diagnosis [4]. To date, four genes (

Notes

References

  1. 1.
    Taglia I, Bonifati V, Mignarri A, Dotti MT, Federico A (2015) Primary familial brain calcification: update on molecular genetics. Neurol Sci 36:787–794.  https://doi.org/10.1007/s10072-015-2110-8 CrossRefPubMedGoogle Scholar
  2. 2.
    Nicolas G, Charbonnier C, Campion D, Veltman JA (2018) Estimation of minimal disease prevalence from population genomic data: application to primary familial brain calcification. Am J Med Genet B Neuropsychiatr Genet 177:68–74.  https://doi.org/10.1002/ajmg.b.32605 CrossRefPubMedGoogle Scholar
  3. 3.
    Manyam BV (2005) What is and what is not ‘Fahr’s disease. Parkinsonism Relat Disord 11:73–80.  https://doi.org/10.1016/j.parkreldis.2004.12.001 CrossRefPubMedGoogle Scholar
  4. 4.
    Batla A, Tai XY, Schottlaender L, Erro R, Balint B, Bhatia KP (2017) Deconstructing Fahr’s disease/syndrome of brain calcification in the era of new genes. Parkinsonism Relat Disord 37:1–10.  https://doi.org/10.1016/j.parkreldis.2016.12.024 CrossRefPubMedGoogle Scholar
  5. 5.
    Rubino E, Giorgio E, Godani M et al (2017) Three novel missense mutations in SLC20A2 associated with idiopathic basal ganglia calcification. J Neurol Sci 377:62–64.  https://doi.org/10.1016/j.jns.2017.03.053
  6. 6.
    López-Villegas D, Kulisevsky J, Deus J et al (1996) Neuropsychological alterations in patients with computed tomography-detected basal ganglia calcification. Arch Neurol 53:251–256.  https://doi.org/10.1001/archneur.1996.00550030061023 CrossRefPubMedGoogle Scholar
  7. 7.
    Richards S, Aziz N, Bale S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405–423.  https://doi.org/10.1038/gim.2015.30 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Wang C, Li Y, Shi L, Ren J et al (2012) Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis. Nat Genet 44:254–256.  https://doi.org/10.1038/ng.1077
  9. 9.
    Legati A, Giovannini D, Nicolas G et al (2015) Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nat Genet 47:579–581.  https://doi.org/10.1038/ng.3289
  10. 10.
    Keller A, Westenberger A, Sobrido A et al (2013) Mutations in the gene encoding PDGF-B cause brain calcifications in humans and mice. Nat Genet 45:1077–1082.  https://doi.org/10.1038/ng.2723 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Larsen FT, Jensen N, Autzen JK, Kongsfelt IB, Pedersen L (2017) Primary brain calcification causal PiT2 transport-knockout variants can exert dominant negative effects on wild-type PiT2 transport function in mammalian cells. J Mol Neurosci 61:215–220.  https://doi.org/10.1007/s12031-016-0868-7 CrossRefPubMedGoogle Scholar
  12. 12.
    Nicolas G, Charbonnier C, de Lemos RR et al (2015) Brain calcification process and phenotypes according to age and sex: Lessons from SLC20A2, PDGFB, and PDGFRB mutation carriers. Am J Med Genet B Neuropsychiatr Genet 168:586–594.  https://doi.org/10.1002/ajmg.b.32336

Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  1. 1.Dipartimento di Scienze Mediche Chirurgiche Neurologiche Metaboliche e dell’InvecchiamentoUniversità degli studi della Campania Luigi VanvitelliNaplesItaly
  2. 2.Dipartimento di Scienze Biomediche AvanzateUniversità degli Studi di Napoli Federico IINaplesItaly
  3. 3.Research & Innovation srl (R&I Genetics)PadovaItaly

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