title: Hereditary spastic paraplegia: clinical genomics and pharmacogenetic perspectives.
abstract: Hereditary spastic paraplegias (HSPs) are a group of single-gene disorders characterised by degeneration of the corticospinal tract axons, leading to bilateral, symmetrical, slowly-progressive spastic paraparesis, predominantly of the lower extremities. So far, ~ 30 different chromosomal HSP loci have been identified by genetic linkage analysis. Defects in intracellular trafficking and transport in myelination and abnormalities of mitochondrial proteins have been involved in HSP pathogenesis. At present, treatment of the HSPs is primarily directed symptomatically toward reducing muscle spasticity. Yet, recent progresses in the identification of HSP mutations are providing formidable tools to pharmacogenetic approaches of drug discovery, validation and prediction of individual response.
authors.forename: Gianmarco
authors.initials: G
authors.lastname: Contino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
mesh_terms: D001418:Baclofen / Q000627:therapeutic use; D018755:GABA Agonists / Q000627:therapeutic use; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D010597:Pharmacogenetics; D015419:Spastic Paraplegia, Hereditary / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology
chemical_list: D018755:GABA Agonists; D001418:Baclofen