A Mild PUM1 Mutation Is Associated with Adult-Onset Ataxia, whereas Haploinsufficiency Causes Developmental Delay and Seizures

Publication date: 22 February 2018 Source:Cell, Volume 172, Issue 5 Author(s): Vincenzo A. Gennarino, Elizabeth E. Palmer, Laura M. McDonell, Li Wang, Carolyn J. Adamski, Amanda Koire, Lauren See, Chun-An Chen, Christian P. Schaaf, Jill A. Rosenfeld, Jessica A. Panzer, Ute Moog, Shuang Hao, Ann Bye, Edwin P. Kirk, Pawel Stankiewicz, Amy M. Breman, Arran McBride, Tejaswi Kandula, Holly A. Dubbs, Rebecca Macintosh, Michael Cardamone, Ying Zhu, Kevin Ying, Kerith-Rae Dias, Megan T. Cho, Lindsay B. Henderson, Berivan Baskin, Paula Morris, Jiang Tao, Mark J. Cowley, Marcel E. Dinger, Tony Roscioli, Oana Caluseriu, Oksana Suchowersky, Rani K. Sachdev, Olivier Lichtarge, Jianrong Tang, Kym M. Boycott, J. Lloyd Holder, Huda Y. Zoghbi Certain mutations can cause proteins to accumulate in neurons, leading to neurodegeneration. We recently showed, however, that upregulation of a wild-type protein, Ataxin1, caused by haploinsufficiency of its repressor, the RNA-binding protein Pumilio1 (PUM1), also causes neurodegeneration in mice. We therefore searched for human patients with PUM1 mutations. We identified eleven individuals with either PUM1 deletions or de novo missense variants who suffer a developmental syndrome (Pumilio1-associated developmental disability, ataxia, and seizure; PADDAS). We also identified a milder missense mutation in a family with adult-onset ataxia with incomplete penetrance (Pumilio1-related cerebellar ataxia, PRCA). Stu...
Source: Cell - Category: Cytology Source Type: research