title: The molecular genetics of non-ALS motor neuron diseases.
abstract: Hereditary disorders of voluntary motor neurons are individually relatively uncommon, but have the potential to provide significant insights into motor neuron function in general and into the mechanisms underlying the more common form of sporadic Amyotrophic Lateral Sclerosis. Recently, mutations in a number of novel genes have been associated with Lower Motor Neuron (HSPB1, HSPB8, GARS, Dynactin), Upper Motor Neuron (Spastin, Atlastin, Paraplegin, HSP60, KIF5A, NIPA1) or mixed ALS-like phenotypes (Alsin, Senataxin, VAPB, BSCL2). In comparison to sporadic ALS these conditions are usually associated with slow progression, but as experience increases, a wide variation in clinical phenotype has become apparent. At the molecular level common themes are emerging that point to areas of specific vulnerability for motor neurons such as axonal transport, endosomal trafficking and RNA processing. We review the clinical and molecular features of this diverse group of genetically determined conditions and consider the implications for the broad group of motor neuron diseases in general.
authors.affiliation: Department of Physiology, Anatomy and Genetics, Oxford University, Oxford, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: James
authors.forename: Kevin
authors.initials: K
authors.lastname: Talbot
mesh_terms: D000293:Adolescent; D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D000818:Animals; D001370:Axonal Transport; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D018832:Molecular Chaperones; D016472:Motor Neuron Disease / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D009132:Muscles / Q000473:pathology; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction; D013577:Syndrome
chemical_list: C432679:BSCL2 protein, human; D044388:GTP-Binding Protein gamma Subunits; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins