Atlastin1 Mutations Are Frequent in Young-Onset Autosomal Dominant Spastic Paraplegia

Abstract
Hereditary spastic paraplegias (HSP) are characterized by progressive lower limb spasticity. It is useful for clinicians to distinguish pure from complex forms. Pure forms are characterized by lower limb spasticity and weakness that are sometimes associated, later in the evolution of the disease, with sphincter disturbances, minor vibration sense loss, and minimal cerebellar ataxia of the upper limbs, whereas complex forms include 1 or more neurological or extraneurological signs that are highly variable.1 Recent genetic studies revealed that these neurodegenerative disorders are genetically very heterogeneous. At least 24 loci have been associated with autosomal dominant or recessive, or X chromosome–linked transmission.2,3 Only 10 of the responsible genes have been identified. Recent studies have demonstrated that the functions of several of these genes are related to axonal transport or intracellular trafficking. This could account for the selective degeneration of neurons with long axons, such as the pyramidal tract.3,4