title: Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum.
abstract: Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a common and clinically distinct form of familial spastic paraplegia that is linked to the SPG11 locus on chromosome 15 in most affected families. We analyzed 12 ARHSP-TCC families, refined the SPG11 candidate interval and identified ten mutations in a previously unidentified gene expressed ubiquitously in the nervous system but most prominently in the cerebellum, cerebral cortex, hippocampus and pineal gland. The mutations were either nonsense or insertions and deletions leading to a frameshift, suggesting a loss-of-function mechanism. The identification of the function of the gene will provide insight into the mechanisms leading to the degeneration of the corticospinal tract and other brain structures in this frequent form of ARHSP.
authors.affiliation: INSERM, UMR679, Federal Institute for Neuroscience Research, Pitié-Salpêtrière Hospital, Paris, France. stevanin@ccr.jussieu.fr
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stevanin
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: Hamid
authors.initials: H
authors.lastname: Azzedine
authors.forename: Paula
authors.initials: P
authors.lastname: Coutinho
authors.forename: Jacques
authors.initials: J
authors.lastname: Chomilier
authors.forename: Paola S
authors.initials: PS
authors.lastname: Denora
authors.forename: Elodie
authors.initials: E
authors.lastname: Martin
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Ouvrard-Hernandez
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tessa
authors.forename: Naïma
authors.initials: N
authors.lastname: Bouslam
authors.forename: Alexander
authors.initials: A
authors.lastname: Lossos
authors.forename: Perrine
authors.initials: P
authors.lastname: Charles
authors.forename: José L
authors.initials: JL
authors.lastname: Loureiro
authors.forename: Nizar
authors.initials: N
authors.lastname: Elleuch
authors.forename: Christian
authors.initials: C
authors.lastname: Confavreux
authors.forename: Vítor T
authors.initials: VT
authors.lastname: Cruz
authors.forename: Merle
authors.initials: M
authors.lastname: Ruberg
authors.forename: Eric
authors.initials: E
authors.lastname: Leguern
authors.forename: Djamel
authors.initials: D
authors.lastname: Grid
authors.forename: Meriem
authors.initials: M
authors.lastname: Tazir
authors.forename: Bertrand
authors.initials: B
authors.lastname: Fontaine
authors.forename: Alessandro
authors.initials: A
authors.lastname: Filla
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002540:Cerebral Cortex / Q000378:metabolism; D002648:Child; D002522:Chlorocebus aethiops; D002884:Chromosomes, Human, Pair 15; D003337:Corpus Callosum / Q000473:pathology*; D004252:DNA Mutational Analysis; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000473:pathology*
chemical_list: D011506:Proteins; C520412:SPG11 protein, human