title: Spastic paraplegia with thin corpus callosum: description of 20 new families, refinement of the SPG11 locus, candidate gene analysis and evidence of genetic heterogeneity.
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.
authors.affiliation: INSERM U679, Salpetriere Hospital, 47 Boulevard de l'Hôpital, 75013 Paris, France. stevanin@ccr.jussieu.fr
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stevanin
authors.forename: Giorgia
authors.initials: G
authors.lastname: Montagna
authors.forename: Hamid
authors.initials: H
authors.lastname: Azzedine
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Valentina
authors.initials: V
authors.lastname: Scarano
authors.forename: Naima
authors.initials: N
authors.lastname: Bouslam
authors.forename: Denise
authors.initials: D
authors.lastname: Cassandrini
authors.forename: Paola S
authors.initials: PS
authors.lastname: Denora
authors.forename: Chiara
authors.initials: C
authors.lastname: Criscuolo
authors.forename: Soraya
authors.initials: S
authors.lastname: Belarbi
authors.forename: Antonio
authors.initials: A
authors.lastname: Orlacchio
authors.forename: Philippe
authors.initials: P
authors.lastname: Jonveaux
authors.forename: Gabriella
authors.initials: G
authors.lastname: Silvestri
authors.forename: Anne Marie Ouvrad
authors.initials: AM
authors.lastname: Hernandez
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Michele
authors.forename: Meriem
authors.initials: M
authors.lastname: Tazir
authors.forename: Caterina
authors.initials: C
authors.lastname: Mariotti
authors.forename: Knut
authors.initials: K
authors.lastname: Brockmann
authors.forename: Alessandro
authors.initials: A
authors.lastname: Malandrini
authors.forename: Marjo S
authors.initials: MS
authors.lastname: van der Knapp
authors.forename: Marcella
authors.initials: M
authors.lastname: Neri
authors.forename: Hassan
authors.initials: H
authors.lastname: Tonekaboni
authors.forename: Mariarosa A B
authors.initials: MA
authors.lastname: Melone
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tessa
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Dotti
authors.forename: Michela
authors.initials: M
authors.lastname: Tosetti
authors.forename: Flavia
authors.initials: F
authors.lastname: Pauri
authors.forename: Antonio
authors.initials: A
authors.lastname: Federico
authors.forename: Carlo
authors.initials: C
authors.lastname: Casali
authors.forename: Vitor T
authors.initials: VT
authors.lastname: Cruz
authors.forename: José L
authors.initials: JL
authors.lastname: Loureiro
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.forename: Sylvie
authors.initials: S
authors.lastname: Forlani
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Paula
authors.initials: P
authors.lastname: Coutinho
authors.forename: Alessandro
authors.initials: A
authors.lastname: Filla
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002884:Chromosomes, Human, Pair 15; D003241:Consanguinity; D003337:Corpus Callosum / Q000473:pathology*; D005260:Female; D005808:Genes, Recessive; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D008126:Lod Score; D008297:Male; D010375:Pedigree; D010641:Phenotype; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000473:pathology*