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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with thin corpus callosum, cognitive decline and lower motor neuron degeneration
Brain, Volume 131, No. 3, Year 2008
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Description
Hereditary spastic paraplegias (HSP) are neurodegenerative diseases mainly characterized by lower limb spasticity associated, in complicated forms, with additional neurological signs. We have analysed a large series of index patients (n = 76) with this condition, either from families with an autosomal recessive inheritance (n = 43) or isolated patients (n = 33), for mutations in the recently identified SPG11 gene. We found 22 truncating mutations, including the first four splice-site mutations, segregating in seven isolated cases and 13 families. Nineteen mutations were novel. Two recurrent mutations were found in Portuguese and North-African patients indicating founder effects in these populations. The mutation frequency varied according to the phenotype, from 41%, in HSP patients presenting with a thin corpus callosum (TCC) visualized by MRI, to 4.5%, in patients with mental impairment without a TCC. Disease onset occurred during the first to the third decade mainly by problems with gait and/or mental retardation. After a mean disease duration of 14.9 ± 6.6 years, the phenotype of 38 SPG11 patients was severe with 53% of patients wheelchair bound or bedridden. In addition to mental retardation, 80% of the patients showed cognitive decline with executive dysfunction. Interestingly, the phenotype also frequently included lower motor neuron degeneration (81%) with wasting (53%). Slight ocular cerebellar signs were also noted in patients with long disease durations. In addition to a TCC (95%), brain MRI revealed white matter alterations (69%) and cortical atrophy (81%), which worsened with disease duration. In conclusion, our study reveals the high frequency of SPG11 mutations in patients with HSP, a TCC and cognitive impairment, including in isolated patients, and extends the associated phenotype. © The Author (2007). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
Authors & Co-Authors
Stévanin, Giovanni
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Azzedine, Hamid
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Angers
Chu Angers
Denora, Paola Silvia
France, Paris
Inserm
France, Paris
Sorbonne Université
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
Boukhris, Amir
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Tunisia, Sfax
Chu Habib Bourguiba
Tazir, Mériem
Algeria, Algiers
Centre Hospitalo-universitaire de Mustapha Bacha
Lossos, Alexander
Israel, Jerusalem
Hadassah University Medical Centre
Rosa, Alberto L.
Argentina, Cordoba
Sanatorio Allende
Lerer, Israela
Israel, Jerusalem
Hadassah University Medical Centre
Hamri, Abdelmadjid
Algeria, Constantine
Centre Hospitalo-universitaire dr Benbadis Constantine
Alegria, Paulo
Portugal, Lisbon
Centro Hospitalar de Lisboa Ocidental Hospital de Egas Moniz
Loureiro, José Leal
Portugal, Santa Maria da Feira
Hospital so Sebastio
Tada, Masayoshi
Japan, Niigata
Niigata University
Hannequin, Didier
France, Rouen
Chu Rouen Normandie
France, Paris
Inserm
Anheim, Mathieu
France, Strasbourg
Hopital Civil
Goizet, Cyril
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Bordeaux
Groupe Hospitalier Pellegrin
González-Martínez, Victoria
France, Montpellier
Hopital Gui de Chauliac
Le Ber, Isabelle
France, Paris
Inserm
France, Paris
Sorbonne Université
Forlani, Sylvie
France, Paris
Inserm
France, Paris
Sorbonne Université
Iwabuchi, Kiyoshi
Japan, Yokohama
Yokohama Neurology Clinic
Meiner, Vardiella L.
Israel, Jerusalem
Hadassah University Medical Centre
Uyanık, Gökhan
Germany, Regensburg
Universität Regensburg
Erichsen, Anne Kjersti
Norway, Oslo
Ulleval University Hospital
Feki, Imed
Tunisia, Sfax
Chu Habib Bourguiba
Pasquier, Florence
France, Lille
Chu Lille
Belarbi, Soraya
Algeria, Algiers
Centre Hospitalo-universitaire de Mustapha Bacha
Tedim Cruz, Vítor Tedim
Portugal, Santa Maria da Feira
Hospital so Sebastio
Depienne, Christel
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Truchetto, Jérémy
France, Paris
Inserm
France, Paris
Sorbonne Université
Garrigues, Guillaume
France, Montpellier
Hopital Gui de Chauliac
Tallaksen, Chantal Me E.
Norway, Oslo
Ulleval University Hospital
Tranchant, Christine H.
France, Strasbourg
Hopital Civil
Nishizawa, Masatoyo
Japan, Niigata
Niigata University
Vale, José
Portugal, Lisbon
Centro Hospitalar de Lisboa Ocidental Hospital de Egas Moniz
Coutinho, Paula
Portugal, Santa Maria da Feira
Hospital so Sebastio
Santorelli, Filippo Maria
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
Mhiri, Chokri
Tunisia, Sfax
Chu Habib Bourguiba
Brice, Alexis
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Dürr, Alexandra
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Statistics
Citations: 213
Authors: 38
Affiliations: 21
Identifiers
Doi:
10.1093/brain/awm293
e-ISSN:
14602156
Research Areas
Cancer
Genetics And Genomics