Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration

Julie Van Der Zee, Tim Van Langenhove, Gabor G. Kovacs, Lubina Dillen, William Deschamps, Sebastiaan Engelborghs, Radoslav Matěj, Mathieu Vandenbulcke, Anne Sieben, Bart Dermaut, Katrien Smets, Philip Van Damme, Céline Merlin, Annelies Laureys, Marleen Van Den Broeck, Maria Mattheijssens, Karin Peeters, Luisa Benussi, Giuliano Binetti, Roberta GhidoniBarbara Borroni, Alessandro Padovani, Silvana Archetti, Pau Pastor, Cristina Razquin, Sara Ortega-Cubero, Isabel Hernández, Mercè Boada, Agustín Ruiz, Alexandre De Mendonça, Gabriel Miltenberger-Miltényi, Frederico Simões Do Couto, Sandro Sorbi, Benedetta Nacmias, Silvia Bagnoli, Caroline Graff, Huei Hsin Chiang, Håkan Thonberg, Robert Perneczky, Janine Diehl-Schmid, Panagiotis Alexopoulos, Giovanni B. Frisoni, Christian Bonvicini, Matthis Synofzik, Walter Maetzler, Jennifer Müller Vom Hagen, Ludger Schöls, Tobias B. Haack, Tim M. Strom, Holger Prokisch, Oriol Dols-Icardo, Jordi Clarimón, Alberto Lleó, Isabel Santana, Maria Rosário Almeida, Beatriz Santiago, Michael T. Heneka, Frank Jessen, Alfredo Ramirez, Raquel Sanchez-Valle, Albert Llado, Ellen Gelpi, Stayko Sarafov, Ivailo Tournev, Albena Jordanova, Eva Parobkova, Gian Maria Fabrizi, Silvia Testi, Eric Salmon, Thomas Ströbel, Patrick Santens, Wim Robberecht, Peter De Jonghe, Jean Jacques Martin, Patrick Cras, Rik Vandenberghe, Peter Paul De Deyn, Marc Cruts, Kristel Sleegers, Christine Van Broeckhoven

Research output: Contribution to journalArticle

Abstract

Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In the present study, we analyzed the SQSTM1 coding sequence for mutations in an extended cohort of 1,808 patients with frontotemporal lobar degeneration (FTLD), ascertained within the European Early-Onset Dementia consortium. As control dataset, we sequenced 1,625 European control individuals and analyzed whole-exome sequence data of 2,274 German individuals (total n = 3,899). Association of rare SQSTM1 mutations was calculated in a meta-analysis of 4,332 FTLD and 10,240 control alleles. We identified 25 coding variants in FTLD patients of which 10 have not been described. Fifteen mutations were absent in the control individuals (carrier frequency

Original languageEnglish
Pages (from-to)397-410
Number of pages14
JournalActa Neuropathologica
Volume128
Issue number3
DOIs
Publication statusPublished - 2014

Keywords

  • ALS
  • FTLD
  • p62
  • Rare variants
  • Sequestosome 1
  • SQSTM1

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Fingerprint Dive into the research topics of 'Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration'. Together they form a unique fingerprint.

  • Cite this

    Van Der Zee, J., Van Langenhove, T., Kovacs, G. G., Dillen, L., Deschamps, W., Engelborghs, S., Matěj, R., Vandenbulcke, M., Sieben, A., Dermaut, B., Smets, K., Van Damme, P., Merlin, C., Laureys, A., Van Den Broeck, M., Mattheijssens, M., Peeters, K., Benussi, L., Binetti, G., ... Van Broeckhoven, C. (2014). Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration. Acta Neuropathologica, 128(3), 397-410. https://doi.org/10.1007/s00401-014-1298-7