Spastic paraplegia with thin corpus callosum: Description of 20 new families, refinement of the SPG11 locus, candidate gene analysis and evidence of genetic heterogeneity

Giovanni Stevanin, Giorgia Montagna, Hamid Azzedine, Enza Maria Valente, Alexandra Durr, Valentina Scarano, Naima Bouslam, Denise Cassandrini, Paola S. Denora, Chiara Criscuolo, Soraya Belarbi, Antonio Orlacchio, Philippe Jonveaux, Gabriella Silvestri, Anne Marie Ouvrad Hernandez, Giuseppe De Michele, Meriem Tazir, Caterina Mariotti, Knut Brockmann, Alessandro MalandriniMarjo S. Van Der Knapp, Marcella Neri, Hassan Tonekaboni, Mariarosa A.B. Melone, Alessandra Tessa, M. Teresa Dotti, Michela Tosetti, Flavia Pauri, Antonio Federico, Carlo Casali, Vitor T. Cruz, José L. Loureiro, Federico Zara, Sylvie Forlani, Enrico Bertini, Paula Coutinho, Alessandro Filla, Alexis Brice, Filippo M. Santorelli*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)149-156
Number of pages8
JournalNeurogenetics
Volume7
Issue number3
DOIs
Publication statusPublished - Jul 2006

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