13 January 2021
Rogue gene implicated in hereditary spastic paraplegia
Published online 26 May 2016
Scientists hope this will expand treatment options.
Biologists have identified gene mutations that cause hereditary spastic paraplegia (HSP), a group of inherited disorders that cause progressive weakness and stiffness of the leg muscles. The discovery can potentially improve genetic screening and therapy.
More than 70 genes are suspected to be responsible for HSP, but their exact roles in this disease remain unknown.
By sequencing the genomes of individuals living with HSP, the scientists from McGill University, Canada, and Mohammed V University, Morocco, homed in on mutations in a gene known as CAPN1 that encodes calpain 1, a calcium-activated protein widely found in the brain1.
One of these mutations eventually leads to a buildup of inactive calpain 1 in the brain.
Inactivating genes similar to CAPN1 in worms, fruit flies, and zebrafish embryos produced the effects of HSP in these animals, confirming the link between CAPN1 gene mutations and HSP.
Discovery of HSP-related genes opens up possibilities for selecting healthy embryos through genetic diagnosis in affected families, the researchers say.
“Besides the prospect of [improved] therapies and the CAPN1’s roles in HSP, this research highlights the importance of calpains in the nervous system,” says Ziv Gan-Or, the lead author of the study.
- Gan-Or, Z. et al. Mutations in CAPN1 cause autosomal-recessive hereditary spastic paraplegia. Am. J. Hum. Genet. 98, 1038–1146 (2016).