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

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Abstract
We evaluated the genetic contribution of the T cell-erestricted 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.
Keywords
Amyotrophic lateral sclerosis (ALS), Frontotemporal dementia (FTD), TAR DNA-Binding protein 43 (TDP-43), T cellerestricted intracellular antigen-1 gene (TIA1), AMYOTROPHIC-LATERAL-SCLEROSIS, FRONTOTEMPORAL DEMENTIA

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Chicago
Baradaran-Heravi, Yalda, Lubina Dillen, Hung Phuoc Nguyen, Sara Van Mossevelde, Jonathan Baets, Peter De Jonghe, Sebastiaan Engelborghs, et al. 2018. “No Supportive Evidence for TIA1 Gene Mutations in a European Cohort of ALS-FTD Spectrum Patients.” Neurobiology of Aging 69.
APA
Baradaran-Heravi, Yalda, Dillen, L., Nguyen, H. P., Van Mossevelde, S., Baets, J., De Jonghe, P., Engelborghs, S., et al. (2018). No supportive evidence for TIA1 gene mutations in a European cohort of ALS-FTD spectrum patients. NEUROBIOLOGY OF AGING, 69.
Vancouver
1.
Baradaran-Heravi Y, Dillen L, Nguyen HP, Van Mossevelde S, Baets J, De Jonghe P, et al. No supportive evidence for TIA1 gene mutations in a European cohort of ALS-FTD spectrum patients. NEUROBIOLOGY OF AGING. 2018;69.
MLA
Baradaran-Heravi, Yalda, Lubina Dillen, Hung Phuoc Nguyen, et al. “No Supportive Evidence for TIA1 Gene Mutations in a European Cohort of ALS-FTD Spectrum Patients.” NEUROBIOLOGY OF AGING 69 (2018): n. pag. Print.
@article{8574299,
  abstract     = {We evaluated the genetic contribution of the T cell-erestricted 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.},
  articleno    = {293.e9},
  author       = {Baradaran-Heravi, Yalda and Dillen, Lubina and Nguyen, Hung Phuoc and Van Mossevelde, Sara and Baets, Jonathan and De Jonghe, Peter and Engelborghs, Sebastiaan and De Deyn, Peter P and Vandenbulcke, Mathieu and Vandenberghe, Rik and Van Damme, Philip and Cras, Patrick and Salmon, Eric and Synofzik, Matthis and Heutink, Peter and Wilke, Carlo and Simon-Sanchez, Javier and Rojas-Garcia, Ricard and Turon-Sans, Janina and Lle{\'o}, Alberto and Ill{\'a}n-Gala, Ignacio and Clarim{\'o}n, Jordi and Borroni, Barbara and Padovani, Alessandro and Pastor, Pau and Diez-Fairen, Monica and Aguilar, Miquel and Gelpi, Ellen and Sanchez-Valle, Raquel and Borrego-Ecija, Sergi and Matej, Radoslav and Parobkova, Eva and Nacmias, Benedetta and Sorbi, Sandro and Bagnoli, Silvia and de Mendon\c{c}a, Alexandre and Ferreira, Catarina and Fraidakis, Matthew J and Diehl-Schmid, Janine and Alexopoulos, Panagiotis and Almeida, Maria Rosario and Santana, Isabel and Van Broeckhoven, Christine and van der Zee, Juli and BELNEU Consortium, on behalf of the and Sieben, Anne and De Bleecker, Jan and Santens, Patrick},
  issn         = {0197-4580},
  journal      = {NEUROBIOLOGY OF AGING},
  language     = {eng},
  pages        = {3},
  title        = {No supportive evidence for TIA1 gene mutations in a European cohort of ALS-FTD spectrum patients},
  url          = {http://dx.doi.org/10.1016/j.neurobiolaging.2018.05.005},
  volume       = {69},
  year         = {2018},
}

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