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

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

  • Nat Genet. 2007 Mar;39(3):366-72. doi: 10.1038/ng1980.
Giovanni Stevanin 1,  Filippo M Santorelli,  Hamid Azzedine,  Paula Coutinho,  Jacques Chomilier,  Paola S Denora,  Elodie Martin,  Anne-Marie Ouvrard-Hernandez,  Alessandra Tessa,  Naïma Bouslam,  Alexander Lossos,  Perrine Charles,  José L Loureiro,  Nizar Elleuch,  Christian Confavreux,  Vítor T Cruz,  Merle Ruberg,  Eric Leguern,  Djamel Grid,  Meriem Tazir,  Bertrand Fontaine,  Alessandro Filla,  Enrico Bertini,  Alexandra Durr,  Alexis Brice
Affiliations

Affiliation

  • 1 INSERM, UMR679, Federal Institute for Neuroscience Research, Pitié-Salpêtrière Hospital, Paris, France. [email protected]
PMID: 17322883 DOI: 10.1038/ng1980
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.

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