Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia

Abstract
The hereditary spastic paraplegias (HSPs; Strümpell-Lorrain syndrome, MIM number 18260) are a diverse class of disorders characterized by insidiously progressive lower-extremity spastic weakness (reviewed in refs. 1,​ 2,​ 3). Eight autosomal dominant HSP (ADHSP) loci have been identified, the most frequent of which is that linked to the SPG4 locus on chromosome 2p22 (found in ∼ 42%)1, followed by that linked to the SPG3A locus on chromosome 14q11–q21 (in ∼ 9%)1. Only SPG4 has been identified4 as a causative gene in ADHSP. Its protein (spastin) is predicted to participate in the assembly or function of nuclear protein complexes4. Here we report the identification of mutations in a newly identified GTPase gene, SPG3A, in ADHSP affected individuals.