Spastic paraplegia with thin corpus callosum: description of 20 new families, refinement of the SPG11 locus, candidate gene analysis and evidence of genetic heterogeneity.
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.
Stevanin
Giovanni
G
INSERM U679, Salpetriere Hospital, 47 Boulevard de l'Hôpital, 75013 Paris, France. stevanin@ccr.jussieu.fr
Montagna
Giorgia
G
Azzedine
Hamid
H
Valente
Enza Maria
EM
Durr
Alexandra
A
Scarano
Valentina
V
Bouslam
Naima
N
Cassandrini
Denise
D
Denora
Paola S
PS
Criscuolo
Chiara
C
Belarbi
Soraya
S
Orlacchio
Antonio
A
Jonveaux
Philippe
P
Silvestri
Gabriella
G
Hernandez
Anne Marie Ouvrad
AM
De Michele
Giuseppe
G
Tazir
Meriem
M
Mariotti
Caterina
C
Brockmann
Knut
K
Malandrini
Alessandro
A
van der Knapp
Marjo S
MS
Neri
Marcella
M
Tonekaboni
Hassan
H
Melone
Mariarosa A B
MA
Tessa
Alessandra
A
Dotti
M Teresa
MT
Tosetti
Michela
M
Pauri
Flavia
F
Federico
Antonio
A
Casali
Carlo
C
Cruz
Vitor T
VT
Loureiro
José L
JL
Zara
Federico
F
Forlani
Sylvie
S
Bertini
Enrico
E
Coutinho
Paula
P
Filla
Alessandro
A
Brice
Alexis
A
Santorelli
Filippo M
FM
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*