No supportive evidence for TIA1 gene mutations in a European cohort of ALS-FTD spectrum patients

Yalda Baradaran-Heravi, Lubina Dillen, Hung Phuoc Nguyen, Sara Van Mossevelde, Jonathan Baets, Peter De Jonghe, Sebastiaan Engelborghs, Peter P. De Deyn, Mathieu Vandenbulcke, Rik Vandenberghe, Philip Van Damme, Patrick Cras, Eric Salmon, Matthis Synofzik, Peter Heutink, Carlo Wilke, Javier Simon-Sanchez, Ricard Rojas-Garcia, Janina Turon-Sans, Alberto LleóIgnacio Illán-Gala, Jordi Clarimón, Barbara Borroni, Alessandro Padovani, Pau Pastor, Monica Diez-Fairen, Miquel Aguilar, Ellen Gelpi, Raquel Sanchez-Valle, Sergi Borrego-Ecija, Radoslav Matej, Eva Parobkova, Benedetta Nacmias, Sandro Sorbi, Silvia Bagnoli, Alexandre de Mendonça, Catarina Ferreira, Matthew J. Fraidakis, Janine Diehl-Schmid, Panagiotis Alexopoulos, Maria Rosário Almeida, Isabel Santana, Christine Van Broeckhoven, Julie van der Zee, Johan Goeman, Dirk Nuytten, Anne Sieben, Jan L. De Bleecker, Patrick Santens, Jan Versijpt, Alex Michotte, Adrian Ivanoiu, Olivier Deryck, Bruno Bergmans, Christiana Willems, Nina De Klippel, Dirk Peeters, Silvana Archettim, Elisa Bonomi, Irene Piaceri, Camilla Ferrari, Frederico Simões do Couto, Ana Verdelho, Gabriel Miltenberger-Miltényi

    Research output: Contribution to journalArticleResearchpeer-review

    6 Citations (Scopus)

    Abstract

    © 2018 The Authors We evaluated the genetic contribution of the T cell–restricted intracellular antigen-1 gene (TIA1) in a European cohort of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) patients. Exonic resequencing of TIA1 in 1120 patients (693 FTD, 341 ALS, 86 FTD-ALS) and 1039 controls identified in total 5 rare heterozygous missense variants, affecting the TIA1 low-complexity domain (LCD). Only 1 missense variant, p.Met290Thr, identified in a familial FTD patient with disease onset at 64 years, was absent from controls yet received a combined annotation-dependent depletion score of 11.42. By contrast, 3 of the 4 variants also detected in unaffected controls, p.Val294Glu, p.Gln318Arg, and p.Ala381Thr, had combined annotation-dependent depletion scores greater than 20. Our findings in a large European patient-control series indicate that variants in TIA1 are not a common cause of ALS and FTD. The observation of recurring TIA1 missense variants in unaffected individuals lead us to conclude that the exact genetic contribution of TIA1 to ALS and FTD pathogenesis remains to be further elucidated.
    Original languageEnglish
    Pages (from-to)293.e9-293.e11
    JournalNeurobiology of Aging
    Volume69
    DOIs
    Publication statusPublished - 1 Sep 2018

    Keywords

    • Amyotrophic lateral sclerosis (ALS)
    • Frontotemporal dementia (FTD)
    • T cell–restricted intracellular antigen-1 gene (TIA1)
    • TAR DNA-Binding protein 43 (TDP-43)

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