Neuronal intranuclear inclusion disease is genetically heterogeneous
Zhongbo Chen, Wai Yan Yau, Zane Jaunmuktane, Arianna Tucci, Prasanth Sivakumar, Sarah A. Gagliano Taliun, Chris Turner, Stéphanie Efthymiou, Kristina Ibáñez, Roisin Sullivan, Farah Bibi, Alkyoni Athanasiou‐Fragkouli, Thomas Bourinaris, David Zhang, Tamás Révész, Tammaryn Lashley, Michael DeTure, Dennis W. Dickson, Keith A. Josephs, Ellen Gelpí, Gábor G. Kovács, Glenda M. Halliday, Dominic B. Rowe, Ian P. Blair, Pentti J. Tienari, Anu Suomalainen, Nick C. Fox, Nicholas Wood, Andrew J. Lees, Matti Haltia, John Hardy, Mina Ryten, Jana Vandrovcová, Henry Houlden
Abstract
Neuronal intranuclear inclusion disease (NIID) is a clinically heterogeneous neurodegenerative condition characterized by pathological intranuclear eosinophilic inclusions. A CGG repeat expansion in NOTCH2NLC was recently identified to be associated with NIID in patients of Japanese descent. We screened pathologically confirmed European NIID, cases of neurodegenerative disease with intranuclear inclusions and applied in silico-based screening using whole-genome sequencing data from 20 536 participants in the 100 000 Genomes Project. We identified a single European case harbouring the pathogenic repeat expansion with a distinct haplotype structure. Thus, we propose new diagnostic criteria as European NIID represents a distinct disease entity from East Asian cases.