doi:10.1038/nindia.2014.26 Published online 24 February 2014
Researchers have identified novel genetic mutations that give rise to hereditary spastic paraplegias (HSP), a group of genetic neurodegenerative disorders1 . Such knowledge of genetic mutations will be very useful for developing diagnostic tools and therapies for HSP.
People suffering from HSP exhibit progressive stiffness and contraction (spasticity) in their lower limbs. Although previous studies have identified 22 genes with mutations linked to HSP, most of the underlying causes of HSP remain undetermined.
To detect mutations in the genes underlying HSP, the researchers analysed the genes of 55 families affected by HSP. They identified the genetic basis in about 75% of the cases — greatly increasing the number of mutated genes known to be associated with HSP. They found mutations in 13 genes known to be mutated in HSP.
The study focused on 14 genes not previously implicated in HSP; these genes accounted for 42% of the cases. The mutations in 15 genes (the above-mentioned 14 plus an additional one) were identified in patients presenting a spectrum of HSP symptoms. Three of these genes were found to be mutated in more than one family; all mutations are predicted to be highly deleterious.
To understand the potential roles of these mutated genes in HSP, the researchers profiled their expression across multiple human tissues. The expressions of two the HSP-associated genes were specific to neural tissue, with neurons showing increased susceptibility to genetic mutations.
The researchers say that the rare genetic mutations may converge on a few key biological processes, indicating that many of the known and candidate HSP genes are highly connected. They say that the results of this study will be highly useful for identifying novel candidate genes and pathways, paving the way to discover potential therapeutic targets.