Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum.

Giovanni Stevanin (1, 2) , Filippo M Santorelli (3) , Hamid Azzedine (1) , Paula Coutinho (4) , Jacques Chomilier (5) , Paola S Denora (1) , Elodie Martin (1) , Anne-Marie Ouvrard-Hernandez (6) , Alessandra Tessa (3) , Naïma Bouslam (1) , Alexander Lossos (7) , Perrine Charles (2) , José L Loureiro (8) , Nizar Elleuch (9) , Christian Confavreux (10, 11) , Vítor T Cruz (8) , Merle Ruberg (1) , Eric Leguern (1, 2, 2) , Djamel Grid (12) , Meriem Tazir (13) , Bertrand Fontaine (14) , Alessandro Filla (15) , Enrico Bertini (3) , Alexandra Durr (1) , Alexis Brice (1, 2, 2)

1 Neurologie et thérapeutique expérimentale
2 CHU Pitié-Salpêtrière [AP-HP]
3 Unit of Molecular Medicine
4 UnIGENe
5 IMPMC - Institut de minéralogie et de physique des milieux condensés
6 Département de neurologie
7 Department of Neurology
8 Departamento de Neurologia
9 Department of neurology
10 Hopital Neurologique
11 Service de Neurologie A-Hopital Neurologique Pierre Wertheimer
12 Généthon
13 Service de Neurologie
14 Affections de la Myeline et des Canaux Ioniques Musculaires
15 Department of Neurological Sciences

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.

Domaines: Neurosciences [q-bio.NC]

Giovanni Stevanin, Filippo M Santorelli, Hamid Azzedine, Paula Coutinho, Jacques Chomilier, et al.. Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum.. Nature Genetics, 2007, 39 (3), pp.366-72. ⟨10.1038/ng1980⟩. ⟨hal-00281704⟩