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.

• Klíčová slova
• Amyotrophic lateral sclerosis (ALS), Frontotemporal dementia (FTD), T cell–restricted intracellular antigen-1 gene (TIA1), TAR DNA-Binding protein 43 (TDP-43),
• MeSH
• amyotrofická laterální skleróza genetika   MeSH
• běloši genetika   MeSH
• frekvence genu MeSH
• frontotemporální demence genetika   MeSH
• kohortové studie MeSH
• lidé MeSH
• missense mutace MeSH
• T-buněčný intracelulární antigen 1 genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• T-buněčný intracelulární antigen 1 MeSH
• TIA1 protein, human MeSH Prohlížeč