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, Barbara Borroni, Jordi Clarimón, 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, BELNEU Consortium

Research output: Contribution to journalArticlepeer-review


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
JournalNeurobiology of Aging
Publication statusPublished - Sep 1 2018


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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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