Journal of Molecular Neuroscience

, Volume 43, Issue 3, pp 333–336 | Cite as

Population and Computational Analysis of the MGEA6 P521A Variation as a Risk Factor for Familial Idiopathic Basal Ganglia Calcification (Fahr’s Disease)

  • Roberta R. Lemos
  • Danyllo F. Oliveira
  • Mayana Zatz
  • João R. M. Oliveira


Familial idiopathic basal ganglia calcification, also known as “Fahr’s disease” (FD), is a neuropsychiatric disorder with autosomal dominant pattern of inheritance and characterized by symmetric basal ganglia calcifications and, occasionally, other brain regions. Currently, there are three loci linked to this devastating disease. The first one (IBGC1) is located in 14q11.2-21.3 and the other two have been identified in 2q37 (IBGC2) and 8p21.1-q11.13 (IBGC3). Further studies identified a heterozygous variation (rs36060072) which consists in the change of the cytosine to guanine located at MGEA6/CTAGE5 gene, present in all of the affected large American family linked to IBGC1. This missense substitution, which induces changes of a proline to alanine at the 521 position (P521A), in a proline-rich and highly conserved protein domain was considered a rare variation, with a minor allele frequency (MAF) of 0.0058 at the US population. Considering that the population frequency of a given variation is an indirect indicative of potential pathogenicity, we screened 200 chromosomes in a random control set of Brazilian samples and in two nuclear families, comparing with our previous analysis in a US population. In addition, we accomplished analyses through bioinformatics programs to predict the pathogenicity of such variation. Our genetic screen found no P521A carriers. Polling these data together with the previous study in the USA, we have now a MAF of 0.0036, showing that this mutation is very rare. On the other hand, the bioinformatics analysis provided conflicting findings. There are currently various candidate genes and loci that could be involved with the underlying molecular basis of FD etiology, and other groups suggested the possible role played by genes in 2q37, related to calcium metabolism, and at chromosome 8 (NRG1 and SNTG1). Additional mutagenesis and in vivo studies are necessary to confirm the pathogenicity for variation in the P521A MGEA6.


MGEA6 P521A variation Polymorphism Familial idiopathic basal ganglia calcification Fahr’s disease 



We are deeply indebted to Dr. Cíntia Rocha, Dr. José Luiz de Lima Filho (LIKA), and Dr Constância Ayres (Aggeu Magalhães Research Center) for the support with sequencing experiments. We also thank Dr. Maria Rita Passos Bueno and Lilian Calabró dos Santos (University of São Paulo) for providing the control DNA samples. This study was supported by the following Brazilian funding agencies and academic bureaus: CNPq (Universal 2008-480149/2008-9), PROPESQ-UFPE, CAPES, and FACEPE (APQ-0997-4.01/08) and PIBIC-UFPE. J.R.M.O. holds a research fellowship from the Brazilian National Research Council (CNPq, Brasília, Brazil) and from the John Simon Guggenheim Foundation (New York, USA).


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Roberta R. Lemos
    • 1
  • Danyllo F. Oliveira
    • 1
  • Mayana Zatz
    • 2
  • João R. M. Oliveira
    • 1
    • 3
  1. 1.Keizo Asami Laboratory (LIKA)Federal University of PernambucoRecifeBrazil
  2. 2.Human Genome Study CenterUniversity of São PauloSão PauloBrazil
  3. 3.Neuropsychiatry DepartmentFederal University of Pernambuco (UFPE)RecifeBrazil

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