30 October 2001. An international team lead by John Fink, University of Michigan, has identified a new gene responsible for hereditary spastic paraplegia (HSP). This disorder, which starts in early childhood and can completely paralyze both legs, has been linked to eight unique chromosomal loci, but to date only one, the gene for spastin, has been identified.
The researchers homed in on a locus (SPG3A) on chromosome 14 linked to autosomal dominant HSP (ADHSP). Their analysis of five families, reported in the October 29 Nature Genetics online, allowed the gene to be mapped to within 2.7cM. Subsequent sequencing analysis identified three disease-specific mutations within the predicted ORF of a 558 amino acid protein.
The protein, coined atlastin, presently has no known function but is homologous to human guanylate binding protein 1 (GBP1), a member of the dynamin family of GTPases. These proteins function in membrane trafficking, including receptor-mediated endocytosis and formation of clathrin-coated vesicles, suggesting that atlastin may be involved in the dynamics of neurotransmission.
This gene may provide a new avenue of research into a variety of neurodegenerative disorders including amyotrophic lateral sclerosis (ALS). "In ALS, for example, there is degeneration of the upper motor neurons; in HSP those same exact pathways are affected," Fink said. "The anterior horn cells, which are also damaged in ALS, are affected in HSP, though to a far lesser extent."-Tom Fagan.
Reference:Zhao X, Alvarado D, Rainier S, Lemons R, Hedera P, Weber CH, Tukel T, Apak M, Heiman-Patterson T, Ming L, Bui M, Fink JK. Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia. Nature Genetics 2001 November;(29):326-331. Abstract