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.
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Acknowledgments
The authors gratefully acknowledge the contribution of all the study participants and their family members; without their cooperation, this work would have not been possible. We thank Sara Pedrotti, Clemens Egger, Yuri D’Elia, and Donatella Brunelli for the technical support. The study was supported by the Ministry of Health of the Autonomous Province of Bolzano and the South Tyrolean Sparkasse Foundation.
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The Institute of Genetic Medicine, European Academy Bozen/Bolzano (EURAC) is an affiliated institute of the University of Lübeck, Germany.
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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.
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Volpato, C.B., De Grandi, A., Buffone, E. et al. 2q37 as a Susceptibility Locus for Idiopathic Basal Ganglia Calcification (IBGC) in a Large South Tyrolean Family. J Mol Neurosci 39, 346–353 (2009). https://doi.org/10.1007/s12031-009-9287-3
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DOI: https://doi.org/10.1007/s12031-009-9287-3