Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with thin corpus callosum, cognitive decline and lower motor neuron degeneration.

Giovanni Stevanin, Hamid Azzedine, Paola Denora, Amir Boukhris, Meriem Tazir, Alexander Lossos, Alberto Luis Rosa, Israela Lerer, Abdelmadjid Hamri, Paulo Alegria, José Loureiro, Masayoshi Tada, Didier Hannequin, Mathieu Anheim, Cyril Goizet, Victoria Gonzalez-Martinez, Isabelle Le Ber, Sylvie Forlani, Kiyoshi Iwabuchi, Vardiela Meiner, Goekhan Uyanik, Anne Kjersti Erichsen, Imed Feki, Florence Pasquier, Soreya Belarbi, Vitor T. Cruz, Christel Depienne, Jeremy Truchetto, Guillaume Garrigues, Chantal Tallaksen, Christine Tranchant, Masatoyo Nishizawa, José Vale, Paula Coutinho, Filippo M. Santorelli, Chokri Mhiri, Alexis Brice, Alexandra Durr
Brain. 2007-12-13; 131(3): 772-784
DOI: 10.1093/brain/awm293


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1. Brain. 2008 Mar;131(Pt 3):772-84. Epub 2007 Dec 13.

Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with
thin corpus callosum, cognitive decline and lower motor neuron degeneration.

Stevanin G(1), Azzedine H, Denora P, Boukhris A, Tazir M, Lossos A, Rosa AL,
Lerer I, Hamri A, Alegria P, Loureiro J, Tada M, Hannequin D, Anheim M, Goizet C,
Gonzalez-Martinez V, Le Ber I, Forlani S, Iwabuchi K, Meiner V, Uyanik G,
Erichsen AK, Feki I, Pasquier F, Belarbi S, Cruz VT, Depienne C, Truchetto J,
Garrigues G, Tallaksen C, Tranchant C, Nishizawa M, Vale J, Coutinho P,
Santorelli FM, Mhiri C, Brice A, Durr A; SPATAX consortium.

Author information:
(1)1INSERM, U679, Université Pierre et Marie Curie-Paris 6, UMR S679, Paris,
France.

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.

DOI: 10.1093/brain/awm293
PMID: 18079167 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus