Letter abstract
Nature Genetics 39, 366 - 372 (2007)
Published online: 18 February 2007 | doi:10.1038/ng1980
Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum
Giovanni Stevanin1,2,3,17, Filippo M Santorelli4,17, Hamid Azzedine1,2,17, Paula Coutinho5,6, Jacques Chomilier7, Paola S Denora4, Elodie Martin1,2, Anne-Marie Ouvrard-Hernandez8, Alessandra Tessa4, Naïma Bouslam1,2, Alexander Lossos9, Perrine Charles3, José L Loureiro5,6, Nizar Elleuch1,2, Christian Confavreux10, Vítor T Cruz6, Merle Ruberg1,2, Eric Leguern1,2,3, Djamel Grid11, Meriem Tazir12, Bertrand Fontaine13,14,15, Alessandro Filla16, Enrico Bertini4, Alexandra Durr1,2,3 & Alexis Brice1,2,3,14,15
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.
- INSERM, UMR679, Federal Institute for Neuroscience Research, Pitié-Salpêtrière Hospital, Paris, France.
- Université Pierre et Marie Curie-Paris 6, UMR679, Pitié-Salpêtrière Hospital, Paris, France.
- Assistance Publique–Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Department Cytogenetics and Genetics, Paris, France.
- Unit of Molecular Medicine, IRCCS-Bambino Gesù Children's Hospital, Rome, Italy.
- UnIGENe, University of Porto, Portugal.
- Departamento de Neurologia, Hospital S. Sebastiao, Santa Maria da Feira, Portugal.
- Institut de Minéralogie et de Physique des Milieux Condensés, Paris 6 and 7 Universities, Paris, France.
- Department of Neurology, Centre Hospitalier Universitaire, Grenoble, France.
- Department of Neurology, Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
- Hôpital Neurologique et Neurochirurgical Pierre Wertheimer, Lyon, France.
- Genethon, Evry, France.
- Department of Neurology, Mustapha Hospital, Algiers, Algeria.
- INSERM U546, Salpêtrière Hospital, Paris, France.
- AP-HP, Pitié-Salpêtrière Hospital, Federation of Neurology, Paris, France.
- Université Pierre et Marie Curie-Paris 6, Pitié-Salpêtrière Medical School, Paris, France.
- Department of Neurological Sciences, Federico II University, Naples, Italy.
- These authors contributed equally to this work.
Correspondence to: Giovanni Stevanin1,2,3,17 e-mail: stevanin@ccr.jussieu.fr
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RESEARCH
Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosumNature Genetics Letter (01 Mar 2007)
