Genetics of familial and sporadic amyotrophic lateral sclerosis

AbstractDiseases affecting motor neurons, such as amyotrophic lateral sclerosis (Lou Gerhig's disease), hereditary spastic paraplegia and spinal bulbar muscular atrophy (Kennedy's disease) are a heterogeneous group of chronic progressive diseases and are among the most puzzling yet untreatable illnesses. Over the last decade, identification of mutations in genes predisposing to these disorders has provided the means to better understand their pathogenesis. The discovery 13 years ago of SOD1 mutations linked to ALS, which account for less than 2% of total cases, had a major impact in the field. However, despite intensive research effort, the pathways leading to the specific motor neurons degeneration in the presence of SOD1 mutations have not been fully identified. This review provides an overview of the genetics of both familial and sporadic forms of ALS