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

Recent advances in hereditary spastic paraplegia.

The hereditary spastic paraplegias are a group of rare disorders that are characterized by great clinical and genetic heterogeneity. There has been an exponential increase in the number of HSP loci mapped in recent years, with nine out of the 17 loci reported during the past 2 years. Eight loci have now been identified for the autosomal-dominant form, and seven of these are associated with pure HSP. Spastic paraplegia-4 remains the most frequent locus, and is usually associated with a pure phenotype. Although the corresponding spastin gene was only recently identified, over 50 mutations have been described to date, which renders molecular diagnosis difficult. Five loci are known for autosomal-recessive HSP, and four of these are associated with complex forms, all with different phenotypes. Two genes have been identified: paraplegin and sacsin. Finally, three loci have been identified in X-linked HSP, two of which are complex forms. The genes that encode L1 and PLP were the first to be identified in HSP disorders. Surprisingly, the five genes encode proteins of different families, making understanding and diagnosis of HSP even more difficult. The discovery of new genes should hopefully help to clarify the pathophysiology of these disorders.[1]


  1. Recent advances in hereditary spastic paraplegia. Tallaksen, C.M., Dürr, A., Brice, A. Curr. Opin. Neurol. (2001) [Pubmed]
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