| Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with thin corpus callosum, cognitive decline and lower motor neuron degeneration. | |
| | |
MedLine Citation:
|
PMID: 18079167 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
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; |
Related Documents
:
|
7536477 - Molecular identification of hereditary persistence of fetal hemoglobin type 2 (hpfh typ... 12911937 - Molecular markers in myeloproliferative disorders: from classification to prognosis? 16400417 - Duchenne muscular dystrophy: alpha-dystroglycan immunoexpression in skeletal muscle and... 16324037 - Resistance to cisatracurium in a patient with melas syndrome. 21177837 - Free fatty acids and the metabolic syndrome in patients with obstructive sleep apnoea. 2014287 - Abnormal testicular function: potential of p-31 mr spectroscopy in diagnosis. |
Publication Detail:
|
Type: Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't Date: 2007-12-13 |
Journal Detail:
|
Title: Brain : a journal of neurology Volume: 131 ISSN: 1460-2156 ISO Abbreviation: Brain Publication Date: 2008 Mar |
Date Detail:
|
Created Date: 2008-02-22 Completed Date: 2008-05-01 Revised Date: 2011-11-24 |
Medline Journal Info:
|
Nlm Unique ID: 0372537 Medline TA: Brain Country: England |
Other Details:
|
Languages: eng Pagination: 772-84 Citation Subset: AIM; IM |
Affiliation:
|
1INSERM, U679, Université Pierre et Marie Curie-Paris 6, UMR S679, Paris, France. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adolescent Adult Age of Onset Base Sequence Brain / pathology Child Child, Preschool Cognition Disorders / genetics*, pathology Corpus Callosum / pathology* DNA Mutational Analysis / methods Female Genes, Recessive Genetic Linkage Genotype Humans Intellectual Disability / genetics, pathology Magnetic Resonance Imaging Male Molecular Sequence Data Motor Neuron Disease / genetics, pathology Mutation* Pedigree Phenotype Proteins / genetics* Spastic Paraplegia, Hereditary / genetics*, pathology, psychology |
| Grant Support | |
ID/Acronym/Agency:
|
GGP06188//Telethon |
| Chemical | |
Reg. No./Substance:
|
0/Proteins; 0/SPG11 protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Axonal alpha-synuclein aggregates herald centripetal degeneration of cardiac sympathetic nerve in Pa...
Next Document: Sleep disturbances in school-age children with chronic pain.