After 25 years, the cause of a rare genetic neurological disease has finally been discovered
Spinocerebellar ataxia type 4 (SCA4) is a sporadic syndrome. Symptoms include muscle weakness, difficulty coordinating body movements, which causes a particularly jerky and unsteady gait, and difficulty speaking. The disease has long been known to have a genetic cause. As early as 1996, a link to chromosome 16q was found, but the mutation causing SCA4 remained unknown until now. Using the long single-stranded whole genome sequencing (LR-GS) method, which searched 6 495 genome sequence datasets, scientists finally discovered that a mutation in the ZFHX3 gene was responsible for the disease.
The ZFHX3 gene is located in a region of DNA that contains many repetitive parts, making analysis difficult. Moreover, the mutation itself is one of these repetitive parts. "This mutation is a toxic extended repeat and we think it flips how the cell treats misfolded or misfolded proteins." says neuroscientist Stefan Bolst of the University of Utah.
About 150 000 people in the United States suffer from all types of spinocerebellar ataxia. The number of people with specific type 4 is much lower. Still, new research means that affected people can be tested for the ZFHX3 gene mutation that causes the disease, further allowing scientists to look for new treatment options.