Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia
| Autor: | N, Fonknechten, D, Mavel, P, Byrne, C S, Davoine, C, Cruaud, D, Bönsch, D, Boentsch, D, Samson, P, Coutinho, M, Hutchinson, P, McMonagle, J M, Burgunder, A, Tartaglione, O, Heinzlef, I, Feki, T, Deufel, N, Parfrey, A, Brice, B, Fontaine, J F, Prud'homme, J, Weissenbach, A, Dürr, J, Hazan |
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| Předmět: |
Adult
Spastin Adolescent Genotype Hereditary spastic paraplegia RNA Splicing Molecular Sequence Data Mutation Missense Locus (genetics) Biology medicine Genetics Missense mutation Humans Child Gene Molecular Biology Genetics (clinical) Microtubule severing Aged Genes Dominant Adenosine Triphosphatases Paraplegia Polymorphism Genetic Genetic heterogeneity General Medicine Middle Aged medicine.disease Phenotype Codon Nonsense Mutation Asymptomatic carrier |
| Zdroj: | Scopus-Elsevier |
| Popis: | Autosomal dominant hereditary spastic paraplegia (AD-HSP) is a group of genetically heterogeneous neurodegenerative disorders characterized by pro- gressive spasticity of the lower limbs. Five AD-HSP loci have been mapped to chromosomes 14q, 2p, 15q, 8q and 12q. The SPG4 locus at 2p21-p22 has been shown to account for approximately 40% of all AD-HSP families. SPG4 encoding spastin, a putative nuclear AAA protein, has recently been identified. Here, sequence analysis of the 17 exons of SPG4 in 87 unrelated AD-HSP patients has resulted in the detection of 34 novel mutations. These SPG4 mutations are scattered along the coding region of the gene and include all types of DNA modification including missense (28%), nonsense (15%) and splice site point (26.5%) mutations as well as deletions (23%) and insertions (7.5%). The clinical analysis of the 238 mutation carriers revealed a high proportion of both asymptomatic carriers (14/238) and patients unaware of symptoms (45/238), and permitted the redefinition of this frequent form of AD-HSP. |
| Databáze: | OpenAIRE |
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