Kong, H.E., Lim, J., Linsalata, A., Kang, Y., Malik, I., Allen, E.G., Cao, Y., Shubeck, L., Johnston, R., Huang, Y., Gu, Y., Guo, X., Zwick, M.E., Qin, Z., Wingo, T.S., Juncos, J., Nelson, D.L., Epstein, M.P., Cutler, D.J., Todd, P.K., Sherman, S.L., Warren, S.T., Jin, P. (2022). Identification of PSMB5 as a genetic modifier of fragile X-associated tremor/ataxia syndrome.  Proc. Natl. Acad. Sci. U.S.A. 119(22): e2118124119.

FBrf0253607

Research paper

SignificanceExpansion of 55-200 CGG repeats in the 5' untranslated region of FMR1 predisposes carriers to fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder. FXTAS demonstrates incomplete penetrance, which strongly suggests the presence of genetic modifiers. We performed whole-genome sequencing (WGS) on male premutation carriers (CGG55-200) followed by a functional screen in Drosophila and identified PSMB5 as a strong suppressor of CGG-associated neurodegeneration, thereby presenting a therapeutic strategy for FXTAS.

PMC9295734 (PMC) (EuropePMC)