CAG repeat length is a determinant of the age-at-onset of polyglutamine-related diseases, including Huntington’s disease. Some patients have significantly earlier or later age-at-onset, suggesting the presence of genetic modifier(s). A work in Movement Disorders conducted by Dr. Yijuang Chern’s group, at the Institute of Biomedical Sciences, demonstrated that PIAS1 is a genetic modifier of polyglutamine diseases. The naturally occurring variant PIAS1S510G interacts with mHTT poorly and thus lowers the SUMOylation and accumulation of mHTT. Knock-in of PIAS1S510G ameliorates Huntington’s disease phenotypes in mice. PIAS1 is a drug target for HD.

Article link：https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.28896