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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Hereditary spastic paraplegia: advances in genetic research. Hereditary Spastic Paraplegia Working group.

Hereditary spastic paraplegia (HSP) is a diverse group of inherited disorders characterized by progressive lower-extremity spasticity and weakness. Insight into the genetic basis of these disorders is expanding rapidly. Uncomplicated autosomal dominant, autosomal recessive, and X-linked HSP are genetically heterogeneous: different genes cause clinically indistinguishable disorders. A locus for autosomal recessive HSP is on chromosome 8q. Loci for autosomal dominant HSP have been identified on chromosomes 2p, 14q, and 15q. One locus (Xq22) has been identified for X-linked, uncomplicated HSP and shown to be due to a proteolipoprotein gene mutation in one family. The existence of HSP families for whom these loci are excluded indicates the existence of additional, as yet unidentified HSP loci. There is marked clinical similarity among HSP families linked to each of these loci, suggesting that gene products from HSP loci may participate in a common biochemical cascade, which, if disturbed, results in axonal degeneration that is maximal at the ends of the longest CNS axons. Identifying the single gene defects that cause HSPs distal axonopathy may provide insight into factors responsible for development and maintenance of axonal integrity. We review clinical, genetic, and pathologic features of HSP and present differential diagnosis and diagnostic criteria of this important group of disorders. We discuss polymorphic microsatellite markers useful for genetic linkage analysis and genetic counseling in HSP.[1]


  1. Hereditary spastic paraplegia: advances in genetic research. Hereditary Spastic Paraplegia Working group. Fink, J.K., Heiman-Patterson, T., Bird, T., Cambi, F., Dubé, M.P., Figlewicz, D.A., Fink, J.K., Haines, J.L., Heiman-Patterson, T., Hentati, A., Pericak-Vance, M.A., Raskind, W., Rouleau, G.A., Siddique, T. Neurology (1996) [Pubmed]
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