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 Malandrini, Marjo 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
Neurogenetics. 2006-05-13; 7(3): 149-156
DOI: 10.1007/s10048-006-0044-2

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1. Neurogenetics. 2006 Jul;7(3):149-56. Epub 2006 May 13.

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

Stevanin G(1), Montagna G, Azzedine H, Valente EM, Durr A, Scarano V, Bouslam N,
Cassandrini D, Denora PS, Criscuolo C, Belarbi S, Orlacchio A, Jonveaux P,
Silvestri G, Hernandez AM, De Michele G, Tazir M, Mariotti C, Brockmann K,
Malandrini A, van der Knapp MS, Neri M, Tonekaboni H, Melone MA, Tessa A, Dotti
MT, Tosetti M, Pauri F, Federico A, Casali C, Cruz VT, Loureiro JL, Zara F,
Forlani S, Bertini E, Coutinho P, Filla A, Brice A, Santorelli FM.

Author information:
(1)INSERM U679, Salpetriere Hospital, 47 Boulevard de l’Hôpital, 75013 Paris,
France.

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.

DOI: 10.1007/s10048-006-0044-2
PMID: 16699786 [Indexed for MEDLINE]

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