Coexistence of variants in TBK1 and in other ALS-related genes elucidates an oligogenic model of pathogenesis in sporadic ALS

Paolo Niccolo' Doronzio, Giuseppe Marangi, Marcella Zollino, Mario Sabatelli, Serena Lattante, Amelia Conte, Giulia Bisogni, Daniela Bernardo, Dante Lamberti, Francesco Paolo Apollo, Christian Lunetta, Stefania Scarlino, Laura Pozzi, Nilo Riva

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

9 Citazioni (Scopus)

Abstract

Variants in TBK1 are responsible for a significant proportion of ALS cases. In the present study, we analysed variants in TBK1 extracted by targeted sequencing of 32 genes in a group of 406 Italian ALS patients. We identified 7 different TBK1 variants in 7 sporadic cases, resulting in a frequency of 1.7%. Three patients had missense variants (p.R357Q, p.R358H and p.R724C), one patient had a small deletion (p.E618del) and three had truncating variants (p.Y482*, p.R229*, p.N681*). Notably, we found that 4 patients had an additional variant in ALS related genes: two in OPTN and two in the 3’UTR region of FUS. By studying an independent group of 7 TBK1 mutated patients previously reported, we found another variant in the 3’UTR region of FUS in one patient. The presence of a second variant in TBK1 variant carriers is an interesting finding that needs to be investigated in larger cohorts of patients. These findings suggest that TBK1 belongs to the category of genes conferring a significantly increased risk, but not sufficient to cause disease.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaNeurobiology of Aging
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • amyotrophic lateral sclerosis, TBK1, FUS, OPTN, oligogenicity

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