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. 1–3). 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.
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Acknowledgements
We gratefully acknowledge the technical assistance of C. Deng, L. Nielsen, D. Tokarz, C. Delaney and D. Thomas, the expert secretarial assistance of L. Girbach and the participation of the patients with HSP and their families, without whom our investigations of HSP would not be possible. This research is supported by grants from the Veterans Affairs Merit Review and the National Institutes of Health (NINDS R01NS33645, R01NS36177 and R01NS38713) to J.K.F.
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Zhao, X., Alvarado, D., Rainier, S. et al. Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia. Nat Genet 29, 326–331 (2001). https://doi.org/10.1038/ng758
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DOI: https://doi.org/10.1038/ng758
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