Journal of Molecular Neuroscience

, Volume 39, Issue 3, pp 346–353

2q37 as a Susceptibility Locus for Idiopathic Basal Ganglia Calcification (IBGC) in a Large South Tyrolean Family

  • Claudia Béu Volpato
  • Alessandro De Grandi
  • Ebba Buffone
  • Maurizio Facheris
  • Uwe Gebert
  • Günther Schifferle
  • Rudolf Schönhuber
  • Andrew Hicks
  • Peter P. Pramstaller
Article

DOI: 10.1007/s12031-009-9287-3

Cite this article as:
Volpato, C.B., De Grandi, A., Buffone, E. et al. J Mol Neurosci (2009) 39: 346. doi:10.1007/s12031-009-9287-3

Abstract

Familial idiopathic basal ganglia calcification (FIBGC) is an inherited neurodegenerative disorder characterized by the accumulation of calcium deposits in different brain regions, particularly in the basal ganglia. FIBGC usually follows an autosomal dominant pattern of inheritance. Despite the mapping to chromosome 14q of a susceptibility locus for IBGC (IBCG1) in one family, this locus has been excluded in several others, demonstrating genetic heterogeneity in this disorder. The etiology of this disorder thus remains largely unknown. Using a large extended multigenerational Italian family from South Tyrol with 17 affected in a total of 56 members, we performed a genome-wide linkage analysis in which we were able to exclude linkage to the IBCG1 locus on chromosome 14q and obtain evidence of a novel locus on chromosome 2q37.

Keywords

FamilialBasal gangliaCalcificationLinkageNew locus

Supplementary material

12031_2009_9287_Fig3a_ESM.gif (251 kb)
Figure S3

Results of the genome-wide scan for each chromosome. The dotted line represents the location score for the parametric analysis using affected only. The solid black line represents the location score for the parametric analysis, while the dashed line represents −log10(p value) for the NPL_Pair score statistic. Genetic distance is based on the deCODE Genetic map. Strongest evidence for linkage was at two positions in the genome, at 2q37 (LOD = 2.44 at marker D2S2973) and 11p15.4 (LOD = 3.63 at marker D11S1760). This linkage was shown to be an artifact due to a noninformative marker flanking D11S1760. Once the analysis was repeated after removing the problem marker close to D11S1760 and after further genotyping the marker at this locus, the signal at 11p15 decreased to LOD = −3.04. Haplotype analysis shows that allele 6 (the most frequent in the population) at D11S1760 is present in all of the affected individuals but also in 14 individuals of unknown status and in one healthy.

12031_2009_9287_Fig3b_ESM.gif (167 kb)
Figure S3

Results of the genome-wide scan for each chromosome. The dotted line represents the location score for the parametric analysis using affected only. The solid black line represents the location score for the parametric analysis, while the dashed line represents −log10(p value) for the NPL_Pair score statistic. Genetic distance is based on the deCODE Genetic map. Strongest evidence for linkage was at two positions in the genome, at 2q37 (LOD = 2.44 at marker D2S2973) and 11p15.4 (LOD = 3.63 at marker D11S1760). This linkage was shown to be an artifact due to a noninformative marker flanking D11S1760. Once the analysis was repeated after removing the problem marker close to D11S1760 and after further genotyping the marker at this locus, the signal at 11p15 decreased to LOD = −3.04. Haplotype analysis shows that allele 6 (the most frequent in the population) at D11S1760 is present in all of the affected individuals but also in 14 individuals of unknown status and in one healthy.

12031_2009_9287_MOESM1_ESM.tif (199 kb)
High resolution (TIFF 198 kb)
12031_2009_9287_MOESM2_ESM.tif (144 kb)
High resolution (TIFF 143 kb)

Copyright information

© Humana Press 2009

Authors and Affiliations

  • Claudia Béu Volpato
    • 1
  • Alessandro De Grandi
    • 1
  • Ebba Buffone
    • 2
  • Maurizio Facheris
    • 1
    • 2
  • Uwe Gebert
    • 3
  • Günther Schifferle
    • 4
  • Rudolf Schönhuber
    • 2
  • Andrew Hicks
    • 1
  • Peter P. Pramstaller
    • 1
    • 2
    • 5
  1. 1.Institute of Genetic MedicineEuropean Academy Bozen/Bolzano (EURAC)BolzanoItaly
  2. 2.Department of NeurologyCentral HospitalBolzanoItaly
  3. 3.Department of RadiologyMarienklinikBolzanoItaly
  4. 4.Department of RadiologyCentral HospitalBolzanoItaly
  5. 5.Department of NeurologyUniversity of LübeckLübeckGermany