Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia
| Autor: | Jamilé Hazan, Alexis Brice, Jean Weissenbach, Nuria Fonknechten, François Artiguenave, Bertrand Fontaine, Delphine Mavel, Jean-Marc Burgunder, Roland Heilig, Jean-François Prud'homme, Corinne Cruaud, Valérie Barbe, Laurence Cattolico, Delphine Samson, Philippe Brottier, Patrick Wincker, Caroline Paternotte, Claire-Sophie Davoine, Alexandra Durr |
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| Rok vydání: | 1999 |
| Předmět: |
Candidate gene
Spastin Protein family Positional cloning Sequence analysis Hereditary spastic paraplegia Amino Acid Motifs DNA Mutational Analysis Molecular Sequence Data Locus (genetics) Biology Oxidative Phosphorylation Mice Genetics medicine Animals Humans Amino Acid Sequence RNA Messenger Cloning Molecular Cells Cultured Adenosine Triphosphatases Expressed Sequence Tags Base Sequence Sequence Homology Amino Acid Paraplegin Spastic Paraplegia Hereditary Exons medicine.disease Introns Mitochondria Muscle Mutation Sequence Alignment |
| Zdroj: | Nature Genetics. 23:296-303 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/15472 |
| Popis: | Autosomal dominant hereditary spastic paraplegia (AD-HSP) is a genetically heterogeneous neurodegenerative disorder characterized by progressive spasticity of the lower limbs. Among the four loci causing AD-HSP identified so far, the SPG4 locus at chromosome 2p2-1p22 has been shown to account for 40-50% of all AD-HSP families. Using a positional cloning strategy based on obtaining sequence of the entire SPG4 interval, we identified a candidate gene encoding a new member of the AAA protein family, which we named spastin. Sequence analysis of this gene in seven SPG4-linked pedigrees revealed several DNA modifications, including missense, nonsense and splice-site mutations. Both SPG4 and its mouse orthologue were shown to be expressed early and ubiquitously in fetal and adult tissues. The sequence homologies and putative subcellular localization of spastin suggest that this ATPase is involved in the assembly or function of nuclear protein complexes. |
| Databáze: | OpenAIRE |
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