Abstract
We studied 20 Mediterranean families (40 patients) with autosomal recessive hereditary spastic paraplegia and thin corpus callosum (ARHSP-TCC, MIM 604360) to characterize their clinical and genetic features. In six families (17 patients) of Algerian Italian, Moroccan, and Portuguese ancestry, we found data consistent with linkage to the SPG11 locus on chromosome 15q13–15, whereas, in four families (nine patients of Italian, French, and Portuguese ancestry) linkage to the SPG11 locus could firmly be excluded, reinforcing the notion that ARHSP-TCC is genetically heterogeneous. Patients from linked and unlinked families could not be distinguished on the basis of clinical features alone. In SPG11-linked kindred, haplotype reconstruction allowed significant refinement to 6 cM, of the minimal chromosomal interval, but analysis of two genes (MAP1A and SEMA6D) in this region did not identify causative mutations. Our findings suggest that ARHSP-TCC is the most frequent form of ARHSP in Mediterranean countries and that it is particularly frequent in Italy.
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Acknowledgements
The authors thank Mrs C. J. Wrenn for critically reading and editing the manuscript. This work was financially supported by the Verum Foundation (to AB), the GIS-Rare Diseases Institute (to GS), the Italian Ministry of Health (to FMS and EB), FIRB RBNE01ZK8F_006 (to AF) and RBAUO1RB44_002 (to GDM), the Italian National Institutes of Health (ISS, to FMS), the Agence National pour la Recherche (to AD), and the Pierfranco and Luisa Mariani Foundation ONLUS (to FMS). We are grateful to Nawal Benammar, Nizar Elleuch, Stephan Klebe, Elodie Denis, Rabea Zemourri and the DNA and cell bank of IFR70 for their help. Most families were collected through a European and Mediterranean network for the study of Spastic Paraplegia and spinocerebellar ATAXia (SPATAX, coordinator: A. Durr, Paris, France).
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Oligonucleotide primers used for the mutation analysis of MAP1A and SEMA6D (PDF 61 kb)
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Stevanin, G., Montagna, G., Azzedine, H. et al. Spastic paraplegia with thin corpus callosum: description of 20 new families, refinement of the SPG11 locus, candidate gene analysis and evidence of genetic heterogeneity. Neurogenetics 7, 149–156 (2006). https://doi.org/10.1007/s10048-006-0044-2
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DOI: https://doi.org/10.1007/s10048-006-0044-2