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

Giovanni Stevanin, 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
Nat Genet. 2007-02-18; 39(3): 366-372
DOI: 10.1038/ng1980


Lire sur PubMed

---

Stevanin G(1), Santorelli FM, Azzedine H, Coutinho P, Chomilier J, Denora PS,
Martin E, Ouvrard-Hernandez AM, Tessa A, Bouslam N, Lossos A, Charles P, Loureiro
JL, Elleuch N, Confavreux C, Cruz VT, Ruberg M, Leguern E, Grid D, Tazir M,
Fontaine B, Filla A, Bertini E, Durr A, Brice A.

Author information:
(1)INSERM, UMR679, Federal Institute for Neuroscience Research, Pitié-Salpêtrière
Hospital, Paris, France.

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.

Auteurs Bordeaux Neurocampus