Hereditary Spastic Paraplegia

Abstract
Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous neurodegenerative disease characterized by progressive spasticity and weakness of the lower limbs. To date, 10 loci have been identified in autosomal dominant HSP (ADHSP) and mapped to chromosomes 14q11.2-q24.3 (SPG3A), 2p21-p24 (SPG4), 15q11.1 (SPG6), 16q24.3 (SPG7), 8q23-q24 (SPG8), 10q23.3-q24.1 (SPG9), 12q13 (SPG10), 19q13 (SPG12), 2q24-q34 (SPG13), and 9q33-q34 (SPG19).1 Five causative genes, which encode the proteins atlastin (SPG3A), spastin (SPG4), paraplegin (SPG7), kinesin heavy chain (KIF5A) (SPG10), and mitochondrial chaperonin HSP60 (SPG13), have been identified for 5 of the 10 ADHSP loci.2-6 Spastin, the most common protein mutated in ADHSP, belongs to the so-called AAA family (adenosine triphosphatases associated with diverse cellular activities).3