03 February 2023
The rogue gene behind crippling nerve disease
Published online 20 June 2017
Scientists zero in on a mutated gene that wreaks havoc in the brain and puts its victims in wheelchairs.
Spastic ataxia is a group of neurodegenerative disorders that rob victims of their abilities to walk and run. Barely able to sit, patients end up bound to wheelchairs.
Brain scans reveal defects in a brain region that controls the timing of and the force exerted to produce muscle movements. But for a long time scientists couldn’t pinpoint the exact molecular mechanisms that trigger spastic ataxia.
However, by sequencing the genomes of seven patients from three unrelated families including ones from a Saudi Arabian family, scientists succeeded in identifying mutations in a gene known as NKX6-2. These mutations are implicated in brain cells damage that consequently causes symptoms of spastic ataxia1.
This gene, which encodes NKX6-2 protein, regulates the activity of other genes that help synthesize myelin, a nerve-cell-wrapping fatty substance that aids in signal propagation. Mutations in NKX6-2 gene disrupt myelin formation, hampering signal transmission and slowing the activities of brain cells that control muscle movement.
“Besides revealing a novel function for NKX6-2 in humans, the most immediate translational benefit of this study is the ability to provide a platform for a precise diagnosis of spastic ataxia,” says Fowzan S. Alkuraya, co-author of the study from the King Faisal Specialist Hospital and Research Center, Saudi Arabia.
Studies with mice and artificial set-ups mimicking human conditions show that NKX6-2 helps specific glial cells, a type of supporting cells in the brain, mature. Mutations in NKX6-2 gene, however, put a stopper on this, shrinking cerebellum, a brain region known to control muscle movement and balance.
- Chelban, V. et al. Mutations in NKX6-2 cause progressive spastic ataxia and hypomyelination. Am. J. Hum. Genet. 100, 969-977 (2017)